Daily Papers

Deep generative models have shown significant promise in generating valid 3D molecular structures, with the GEOM-Drugs dataset serving as a key benchmark. However, current evaluation protocols suffer from critical flaws, including incorrect valency definitions, bugs in bond order calculations, and reliance on force fields inconsistent with the reference data. In this work, we revisit GEOM-Drugs and propose a corrected evaluation framework: we identify and fix issues in data preprocessing, construct chemically accurate valency tables, and introduce a GFN2-xTB-based geometry and energy benchmark. We retrain and re-evaluate several leading models under this framework, providing updated performance metrics and practical recommendations for future benchmarking. Our results underscore the need for chemically rigorous evaluation practices in 3D molecular generation. Our recommended evaluation methods and GEOM-Drugs processing scripts are available at https://github.com/isayevlab/geom-drugs-3dgen-evaluation.

Accurate thermochemical data with sub-chemical accuracy (i.e., within pm1 kcal mol^{-1} from sufficiently accurate experimental or theoretical reference data) is essential for the development and improvement of computational chemistry methods. Challenging thermochemical properties such as heats of formation and total atomization energies (TAEs) are of particular interest because they rigorously test the ability of computational chemistry methods to accurately describe complex chemical transformations involving multiple bond rearrangements. Yet, existing thermochemical datasets that confidently reach this level of accuracy are limited in either size or scope. Datasets with highly accurate reference values include a small number of data points, and larger datasets provide less accurate data or only cover a narrow portion of the chemical space. The existing datasets are therefore insufficient for developing data-driven methods with predictive accuracy over a large chemical space. The Microsoft Research Accurate Chemistry Collection (MSR-ACC) will address this challenge. Here, it offers the MSR-ACC/TAE25 dataset of 76,879 total atomization energies obtained at the CCSD(T)/CBS level via the W1-F12 thermochemical protocol. The dataset is constructed to exhaustively cover chemical space for all elements up to argon by enumerating and sampling chemical graphs, thus avoiding bias towards any particular subspace of the chemical space (such as drug-like, organic, or experimentally observed molecules). With this first dataset in MSR-ACC, we enable data-driven approaches for developing predictive computational chemistry methods with unprecedented accuracy and scope.

This paper challenges the recent paradigm in atomic property prediction that links progress to growing dataset sizes and computational resources. We show that pretraining on a carefully selected, task-relevant dataset can match or even surpass large-scale pretraining, while using as little as 1/24th of the computational cost. We introduce the Chemical Similarity Index (CSI), a novel metric inspired by computer vision's Fr\'echet Inception Distance, for molecular graphs which quantifies the alignment between upstream pretraining datasets and downstream tasks. By selecting the most relevant dataset with minimal CSI distance, we show that models pretrained on a smaller, focused dataset consistently outperform those pretrained on massive, mixed datasets such as JMP, even when those larger datasets include the relevant dataset. Counterintuitively, we also find that indiscriminately adding more data can degrade model performance when the additional data poorly aligns with the task at hand. Our findings highlight that quality often outperforms quantity in pretraining for atomic property prediction.

Classical force fields (FF) based on machine learning (ML) methods show great potential for large scale simulations of materials. MLFFs have hitherto largely been designed and fitted for specific systems and are not usually transferable to chemistries beyond the specific training set. We develop a unified atomisitic line graph neural network-based FF (ALIGNN-FF) that can model both structurally and chemically diverse materials with any combination of 89 elements from the periodic table. To train the ALIGNN-FF model, we use the JARVIS-DFT dataset which contains around 75000 materials and 4 million energy-force entries, out of which 307113 are used in the training. We demonstrate the applicability of this method for fast optimization of atomic structures in the crystallography open database and by predicting accurate crystal structures using genetic algorithm for alloys.

Density Functional Theory (DFT) is the most widely used electronic structure method for predicting the properties of molecules and materials. Although DFT is, in principle, an exact reformulation of the Schr\"odinger equation, practical applications rely on approximations to the unknown exchange-correlation (XC) functional. Most existing XC functionals are constructed using a limited set of increasingly complex, hand-crafted features that improve accuracy at the expense of computational efficiency. Yet, no current approximation achieves the accuracy and generality for predictive modeling of laboratory experiments at chemical accuracy -- typically defined as errors below 1 kcal/mol. In this work, we present Skala, a modern deep learning-based XC functional that bypasses expensive hand-designed features by learning representations directly from data. Skala achieves chemical accuracy for atomization energies of small molecules while retaining the computational efficiency typical of semi-local DFT. This performance is enabled by training on an unprecedented volume of high-accuracy reference data generated using computationally intensive wavefunction-based methods. Notably, Skala systematically improves with additional training data covering diverse chemistry. By incorporating a modest amount of additional high-accuracy data tailored to chemistry beyond atomization energies, Skala achieves accuracy competitive with the best-performing hybrid functionals across general main group chemistry, at the cost of semi-local DFT. As the training dataset continues to expand, Skala is poised to further enhance the predictive power of first-principles simulations.

Machine learning (ML) models hold the promise of transforming atomic simulations by delivering quantum chemical accuracy at a fraction of the computational cost. Realization of this potential would enable high-throughout, high-accuracy molecular screening campaigns to explore vast regions of chemical space and facilitate ab initio simulations at sizes and time scales that were previously inaccessible. However, a fundamental challenge to creating ML models that perform well across molecular chemistry is the lack of comprehensive data for training. Despite substantial efforts in data generation, no large-scale molecular dataset exists that combines broad chemical diversity with a high level of accuracy. To address this gap, Meta FAIR introduces Open Molecules 2025 (OMol25), a large-scale dataset composed of more than 100 million density functional theory (DFT) calculations at the omegaB97M-V/def2-TZVPD level of theory, representing billions of CPU core-hours of compute. OMol25 uniquely blends elemental, chemical, and structural diversity including: 83 elements, a wide-range of intra- and intermolecular interactions, explicit solvation, variable charge/spin, conformers, and reactive structures. There are ~83M unique molecular systems in OMol25 covering small molecules, biomolecules, metal complexes, and electrolytes, including structures obtained from existing datasets. OMol25 also greatly expands on the size of systems typically included in DFT datasets, with systems of up to 350 atoms. In addition to the public release of the data, we provide baseline models and a comprehensive set of model evaluations to encourage community engagement in developing the next-generation ML models for molecular chemistry.

Accurate prediction of atomistic, thermodynamic, and kinetic properties from molecular structures underpins materials innovation. Existing computational and experimental approaches lack the scalability required to efficiently navigate chemical space. Scientific foundation models trained on large unlabeled datasets offer a path toward exploring chemical space across diverse application domains. Here we develop MIST, a family of molecular foundation models with up to an order of magnitude more parameters and data than prior works. Trained using a novel tokenization scheme that comprehensively captures nuclear, electronic, and geometric information, MIST learns from a diverse range of molecules. MIST models have been fine-tuned to predict more than 400 structure -- property relationships and match or exceed state-of-the-art performance across benchmarks spanning physiology, electrochemistry, and quantum chemistry. We demonstrate the ability of these models to solve real-world problems across chemical space, including multiobjective electrolyte solvent screening, olfactory perception mapping, isotope half-life prediction, stereochemical reasoning for chiral organometallic compounds, and binary and multi-component mixture property prediction. Probing MIST models using mechanistic interpretability methods reveals identifiable patterns and trends not explicitly present in the training data, suggesting that the models learn generalizable scientific concepts. We formulate hyperparameter-penalized Bayesian neural scaling laws and use them to reduce the computational cost of model development by an order of magnitude. The methods and findings presented here represent a significant step toward accelerating materials discovery, design, and optimization using foundation models and provide valuable guidance for training compute-optimal scientific foundation models.

Generative models for materials, especially inorganic crystals, hold potential to transform the theoretical prediction of novel compounds and structures. Advancement in this field depends critically on robust benchmarks and minimal, information-rich datasets that enable meaningful model evaluation. This paper critically examines common datasets and reported metrics for a crystal structure prediction taskx2014generating the most likely structures given the chemical composition of a material. We focus on three key issues: First, materials datasets should contain unique crystal structures; for example, we show that the widely-utilized carbon-24 dataset only contains approx40% unique structures. Second, materials datasets should not be split randomly if polymorphs of many different compositions are numerous, which we find to be the case for the perov-5 dataset. Third, benchmarks can mislead if used uncritically, e.g., reporting a match rate metric without considering the structural variety exhibited by identical building blocks. To address these oft-overlooked issues, we introduce several fixes. We provide revised versions of the carbon-24 dataset: one with duplicates removed, one deduplicated and split by number of atoms N, and two containing only identical structures but with different unit cells. We also propose a new split for the perov-5 dataset which ensures polymorphs are grouped within each split subset, setting a more sensible standard for benchmarking model performance. Finally, we present METRe and cRMSE, new model evaluation metrics that can correct existing issues with the match rate metric.

Large Language Models (LLMs) have shown growing potential in molecular sciences, but they often produce chemically inaccurate descriptions and struggle to recognize or justify potential errors. This raises important concerns about their robustness and reliability in scientific applications. To support more rigorous evaluation of LLMs in chemical reasoning, we present the MolErr2Fix benchmark, designed to assess LLMs on error detection and correction in molecular descriptions. Unlike existing benchmarks focused on molecule-to-text generation or property prediction, MolErr2Fix emphasizes fine-grained chemical understanding. It tasks LLMs with identifying, localizing, explaining, and revising potential structural and semantic errors in molecular descriptions. Specifically, MolErr2Fix consists of 1,193 fine-grained annotated error instances. Each instance contains quadruple annotations, i.e,. (error type, span location, the explanation, and the correction). These tasks are intended to reflect the types of reasoning and verification required in real-world chemical communication. Evaluations of current state-of-the-art LLMs reveal notable performance gaps, underscoring the need for more robust chemical reasoning capabilities. MolErr2Fix provides a focused benchmark for evaluating such capabilities and aims to support progress toward more reliable and chemically informed language models. All annotations and an accompanying evaluation API will be publicly released to facilitate future research.

Transition state (TS) structures define the critical geometries and energy barriers underlying chemical reactivity, yet their fleeting nature renders them experimentally elusive and drives the reliance on costly, high-throughput density functional theory (DFT) calculations. Here, we introduce TS-GEN, a conditional flow-matching generative model that maps samples from a simple Gaussian prior directly to transition-state saddle-point geometries in a single, deterministic pass. By embedding both reactant and product conformations as conditioning information, TS-GEN learns to transport latent noise to true TS structures via an optimal-transport path, effectively replacing the iterative optimization common in nudged-elastic band or string-method algorithms. TS-GEN delivers unprecedented accuracy, achieving a root-mean-square deviation of 0.004 mathring{A} (vs. 0.103 mathring{A} for prior state-of-the-art) and a mean barrier-height error of 1.019 {rm kcal/mol} (vs. 2.864 {rm kcal/mol}), while requiring only 0.06 {rm s} GPU time per inference. Over 87% of generated TSs meet chemical-accuracy criteria (<1.58 {rm kcal/mol} error), substantially outpacing existing methods. TS-GEN also exhibits strong transferability to out-of-distribution reactions from a larger database. By uniting sub-angstrom precision, sub-second speed, and broad applicability, TS-GEN will be highly useful for high-throughput exploration of complex reaction networks, paving the way to the exploration of novel chemical reaction mechanisms.

We present OrbNet Denali, a machine learning model for electronic structure that is designed as a drop-in replacement for ground-state density functional theory (DFT) energy calculations. The model is a message-passing neural network that uses symmetry-adapted atomic orbital features from a low-cost quantum calculation to predict the energy of a molecule. OrbNet Denali is trained on a vast dataset of 2.3 million DFT calculations on molecules and geometries. This dataset covers the most common elements in bio- and organic chemistry (H, Li, B, C, N, O, F, Na, Mg, Si, P, S, Cl, K, Ca, Br, I) as well as charged molecules. OrbNet Denali is demonstrated on several well-established benchmark datasets, and we find that it provides accuracy that is on par with modern DFT methods while offering a speedup of up to three orders of magnitude. For the GMTKN55 benchmark set, OrbNet Denali achieves WTMAD-1 and WTMAD-2 scores of 7.19 and 9.84, on par with modern DFT functionals. For several GMTKN55 subsets, which contain chemical problems that are not present in the training set, OrbNet Denali produces a mean absolute error comparable to those of DFT methods. For the Hutchison conformers benchmark set, OrbNet Denali has a median correlation coefficient of R^2=0.90 compared to the reference DLPNO-CCSD(T) calculation, and R^2=0.97 compared to the method used to generate the training data (wB97X-D3/def2-TZVP), exceeding the performance of any other method with a similar cost. Similarly, the model reaches chemical accuracy for non-covalent interactions in the S66x10 dataset. For torsional profiles, OrbNet Denali reproduces the torsion profiles of wB97X-D3/def2-TZVP with an average MAE of 0.12 kcal/mol for the potential energy surfaces of the diverse fragments in the TorsionNet500 dataset.

Accurate potential energy surface (PES) descriptions are essential for atomistic simulations of materials. Universal machine learning interatomic potentials (UMLIPs)^{1-3} offer a computationally efficient alternative to density functional theory (DFT)^4 for PES modeling across the periodic table. However, their accuracy today is fundamentally constrained due to a reliance on DFT relaxation data.^{5,6} Here, we introduce MatPES, a foundational PES dataset comprising sim 400,000 structures carefully sampled from 281 million molecular dynamics snapshots that span 16 billion atomic environments. We demonstrate that UMLIPs trained on the modestly sized MatPES dataset can rival, or even outperform, prior models trained on much larger datasets across a broad range of equilibrium, near-equilibrium, and molecular dynamics property benchmarks. We also introduce the first high-fidelity PES dataset based on the revised regularized strongly constrained and appropriately normed (r^2SCAN) functional^7 with greatly improved descriptions of interatomic bonding. The open source MatPES initiative emphasizes the importance of data quality over quantity in materials science and enables broad community-driven advancements toward more reliable, generalizable, and efficient UMLIPs for large-scale materials discovery and design.

Identifying the chemical structure from a graphical representation, or image, of a molecule is a challenging pattern recognition task that would greatly benefit drug development. Yet, existing methods for chemical structure recognition do not typically generalize well, and show diminished effectiveness when confronted with domains where data is sparse, or costly to generate, such as hand-drawn molecule images. To address this limitation, we propose a new chemical structure recognition tool that delivers state-of-the-art performance and can adapt to new domains with a limited number of data samples and supervision. Unlike previous approaches, our method provides atom-level localization, and can therefore segment the image into the different atoms and bonds. Our model is the first model to perform OCSR with atom-level entity detection with only SMILES supervision. Through rigorous and extensive benchmarking, we demonstrate the preeminence of our chemical structure recognition approach in terms of data efficiency, accuracy, and atom-level entity prediction.

Creating a single unified interatomic potential capable of attaining ab initio accuracy across all chemistry remains a long-standing challenge in computational chemistry and materials science. This work introduces a training protocol for foundation machine-learning interatomic potentials (MLIPs) that bridge molecular, surface, and materials chemistry through cross-domain learning. First, we introduce enhancements to the MACE architecture that improve its performance on chemically diverse databases by increasing weight sharing across chemical elements and introducing non-linear factors into the tensor decomposition of the product basis. Second, we develop a multi-head replay post-training methodology that enables efficient knowledge transfer across diverse chemical domains. By fine-tuning on datasets at different levels of electronic structure theory, including inorganic crystals, molecular systems, surface chemistry, and reactive organic chemistry, we demonstrate that a single unified model achieves state-of-the-art performance across several chemical domains. Comprehensive benchmarking reveals superior cross-domain transferability compared with existing specialised and multi-task models, with notable improvements in molecular and surface properties while maintaining state-of-the-art performance in materials-property prediction.

Quantitative chemistry is central to modern chemical research, yet the ability of large language models (LLMs) to perform its rigorous, step-by-step calculations remains underexplored. To fill this blank, we propose QCBench, a Quantitative Chemistry oriented benchmark comprising 350 computational chemistry problems across 7 chemistry subfields, which contains analytical chemistry, bio/organic chemistry, general chemistry, inorganic chemistry, physical chemistry, polymer chemistry and quantum chemistry. To systematically evaluate the mathematical reasoning abilities of large language models (LLMs), they are categorized into three tiers: easy, medium, and difficult. Each problem, rooted in realistic chemical scenarios, is structured to prevent heuristic shortcuts and demand explicit numerical reasoning. QCBench enables fine-grained diagnosis of computational weaknesses, reveals model-specific limitations across difficulty levels, and lays the groundwork for future improvements such as domain-adaptive fine-tuning or multi-modal integration. Evaluations on 24 LLMs demonstrate a consistent performance degradation with increasing task complexity, highlighting the current gap between language fluency and scientific computation accuracy. Code for QCBench is available at https://github.com/jiaqingxie/QCBench.

Accurate prediction of bond dissociation energies (BDEs) underpins mechanistic insight and the rational design of molecules and materials. We present a systematic, reproducible benchmark comparing quantum and classical machine learning models for BDE prediction using a chemically curated feature set encompassing atomic properties (atomic numbers, hybridization), bond characteristics (bond order, type), and local environmental descriptors. Our quantum framework, implemented in Qiskit Aer on six qubits, employs ZZFeatureMap encodings with variational ansatz (RealAmplitudes) across multiple architectures Variational Quantum Regressors (VQR), Quantum Support Vector Regressors (QSVR), Quantum Neural Networks (QNN), Quantum Convolutional Neural Networks (QCNN), and Quantum Random Forests (QRF). These are rigorously benchmarked against strong classical baselines, including Support Vector Regression (SVR), Random Forests (RF), and Multi-Layer Perceptrons (MLP). Comprehensive evaluation spanning absolute and relative error metrics, threshold accuracies, and error distributions shows that top-performing quantum models (QCNN, QRF) match the predictive accuracy and robustness of classical ensembles and deep networks, particularly within the chemically prevalent mid-range BDE regime. These findings establish a transparent baseline for quantum-enhanced molecular property prediction and outline a practical foundation for advancing quantum computational chemistry toward near chemical accuracy.

The ability to quickly and accurately compute properties from atomic simulations is critical for advancing a large number of applications in chemistry and materials science including drug discovery, energy storage, and semiconductor manufacturing. To address this need, Meta FAIR presents a family of Universal Models for Atoms (UMA), designed to push the frontier of speed, accuracy, and generalization. UMA models are trained on half a billion unique 3D atomic structures (the largest training runs to date) by compiling data across multiple chemical domains, e.g. molecules, materials, and catalysts. We develop empirical scaling laws to help understand how to increase model capacity alongside dataset size to achieve the best accuracy. The UMA small and medium models utilize a novel architectural design we refer to as mixture of linear experts that enables increasing model capacity without sacrificing speed. For example, UMA-medium has 1.4B parameters but only ~50M active parameters per atomic structure. We evaluate UMA models on a diverse set of applications across multiple domains and find that, remarkably, a single model without any fine-tuning can perform similarly or better than specialized models. We are releasing the UMA code, weights, and associated data to accelerate computational workflows and enable the community to continue to build increasingly capable AI models.

Recent advances in molecular foundation models have shown impressive performance in molecular property prediction and de novo molecular design, with promising applications in areas such as drug discovery and reaction prediction. Nevertheless, most existing approaches rely exclusively on SMILES representations and overlook both experimental spectra and 3D structural information-two indispensable sources for capturing molecular behavior in real-world scenarios. This limitation reduces their effectiveness in tasks where stereochemistry, spatial conformation, and experimental validation are critical. To overcome these challenges, we propose MolSpectLLM, a molecular foundation model pretrained on Qwen2.5-7B that unifies experimental spectroscopy with molecular 3D structure. By explicitly modeling molecular spectra, MolSpectLLM achieves state-of-the-art performance on spectrum-related tasks, with an average accuracy of 0.53 across NMR, IR, and MS benchmarks. MolSpectLLM also shows strong performance on the spectra analysis task, obtaining 15.5% sequence accuracy and 41.7% token accuracy on Spectra-to-SMILES, substantially outperforming large general-purpose LLMs. More importantly, MolSpectLLM not only achieves strong performance on molecular elucidation tasks, but also generates accurate 3D molecular structures directly from SMILES or spectral inputs, bridging spectral analysis, molecular elucidation, and molecular design. Code are available at https://github.com/Eurekashen/MolSpectLLM{https://github.com/Eurekashen/MolSpectLLM}.

Molecular structure recognition is the task of translating a molecular image into its graph structure. Significant variation in drawing styles and conventions exhibited in chemical literature poses a significant challenge for automating this task. In this paper, we propose MolScribe, a novel image-to-graph generation model that explicitly predicts atoms and bonds, along with their geometric layouts, to construct the molecular structure. Our model flexibly incorporates symbolic chemistry constraints to recognize chirality and expand abbreviated structures. We further develop data augmentation strategies to enhance the model robustness against domain shifts. In experiments on both synthetic and realistic molecular images, MolScribe significantly outperforms previous models, achieving 76-93% accuracy on public benchmarks. Chemists can also easily verify MolScribe's prediction, informed by its confidence estimation and atom-level alignment with the input image. MolScribe is publicly available through Python and web interfaces: https://github.com/thomas0809/MolScribe.

Existing visual parsers for molecule diagrams translate pixel-based raster images such as PNGs to chemical structure representations (e.g., SMILES). However, PDFs created by word processors including LaTeX and Word provide explicit locations and shapes for characters, lines, and polygons. We extract symbols from born-digital PDF molecule images and then apply simple graph transformations to capture both visual and chemical structure in editable ChemDraw files (CDXML). Our fast ( PDF rightarrow visual graph rightarrow chemical graph ) pipeline does not require GPUs, Optical Character Recognition (OCR) or vectorization. We evaluate on standard benchmarks using SMILES strings, along with a novel evaluation that provides graph-based metrics and error compilation using LgEval. The geometric information in born-digital PDFs produces a highly accurate parser, motivating generating training data for visual parsers that recognize from raster images, with extracted graphics, visual structure, and chemical structure as annotations. To do this we render SMILES strings in Indigo, parse molecule structure, and then validate recognized structure to select correct files.

Computational quantum chemistry plays a critical role in drug discovery, chemical synthesis, and materials science. While first-principles methods, such as density functional theory (DFT), provide high accuracy in modeling electronic structures and predicting molecular properties, they are computationally expensive. Machine learning interatomic potentials (MLIPs) have emerged as promising surrogate models that aim to achieve DFT-level accuracy while enabling efficient large-scale atomistic simulations. The development of accurate and transferable MLIPs requires large-scale, high-quality datasets with both energy and force labels. Critically, MLIPs must generalize not only to stable geometries but also to intermediate, non-equilibrium conformations encountered during atomistic simulations. In this work, we introduce PubChemQCR, a large-scale dataset of molecular relaxation trajectories curated from the raw geometry optimization outputs of the PubChemQC project. PubChemQCR is the largest publicly available dataset of DFT-based relaxation trajectories for small organic molecules, comprising approximately 3.5 million trajectories and over 300 million molecular conformations computed at various levels of theory. Each conformation is labeled with both total energy and atomic forces, making the dataset suitable for training and evaluating MLIPs. To provide baselines for future developments, we benchmark nine representative MLIP models on the dataset. Our resources are publicly available at https://huggingface.co/divelab

We present a scheme to obtain an inexpensive and reliable estimate of the uncertainty associated with the predictions of a machine-learning model of atomic and molecular properties. The scheme is based on resampling, with multiple models being generated based on sub-sampling of the same training data. The accuracy of the uncertainty prediction can be benchmarked by maximum likelihood estimation, which can also be used to correct for correlations between resampled models, and to improve the performance of the uncertainty estimation by a cross-validation procedure. In the case of sparse Gaussian Process Regression models, this resampled estimator can be evaluated at negligible cost. We demonstrate the reliability of these estimates for the prediction of molecular energetics, and for the estimation of nuclear chemical shieldings in molecular crystals. Extension to estimate the uncertainty in energy differences, forces, or other correlated predictions is straightforward. This method can be easily applied to other machine learning schemes, and will be beneficial to make data-driven predictions more reliable, and to facilitate training-set optimization and active-learning strategies.

Developing robust representations of chemical structures that enable models to learn topological inductive biases is challenging. In this manuscript, we present a representation of atomistic systems. We begin by proving that our representation satisfies all structural, geometric, efficiency, and generalizability constraints. Afterward, we provide a general algorithm to encode any atomistic system. Finally, we report performance comparable to state-of-the-art methods on numerous tasks. We open-source all code and datasets. The code and data are available at https://github.com/rahulkhorana/PolyatomicComplexes.

Chemical reasoning inherently integrates visual, textual, and symbolic modalities, yet existing benchmarks rarely capture this complexity, often relying on simple image-text pairs with limited chemical semantics. As a result, the actual ability of Multimodal Large Language Models (MLLMs) to process and integrate chemically meaningful information across modalities remains unclear. We introduce ChemVTS-Bench, a domain-authentic benchmark designed to systematically evaluate the Visual-Textual-Symbolic (VTS) reasoning abilities of MLLMs. ChemVTS-Bench contains diverse and challenging chemical problems spanning organic molecules, inorganic materials, and 3D crystal structures, with each task presented in three complementary input modes: (1) visual-only, (2) visual-text hybrid, and (3) SMILES-based symbolic input. This design enables fine-grained analysis of modality-dependent reasoning behaviors and cross-modal integration. To ensure rigorous and reproducible evaluation, we further develop an automated agent-based workflow that standardizes inference, verifies answers, and diagnoses failure modes. Extensive experiments on state-of-the-art MLLMs reveal that visual-only inputs remain challenging, structural chemistry is the hardest domain, and multimodal fusion mitigates but does not eliminate visual, knowledge-based, or logical errors, highlighting ChemVTS-Bench as a rigorous, domain-faithful testbed for advancing multimodal chemical reasoning. All data and code will be released to support future research.

Recent developments in deep learning have made remarkable progress in speeding up the prediction of quantum chemical (QC) properties by removing the need for expensive electronic structure calculations like density functional theory. However, previous methods learned from 1D SMILES sequences or 2D molecular graphs failed to achieve high accuracy as QC properties primarily depend on the 3D equilibrium conformations optimized by electronic structure methods, far different from the sequence-type and graph-type data. In this paper, we propose a novel approach called Uni-Mol+ to tackle this challenge. Uni-Mol+ first generates a raw 3D molecule conformation from inexpensive methods such as RDKit. Then, the raw conformation is iteratively updated to its target DFT equilibrium conformation using neural networks, and the learned conformation will be used to predict the QC properties. To effectively learn this update process towards the equilibrium conformation, we introduce a two-track Transformer model backbone and train it with the QC property prediction task. We also design a novel approach to guide the model's training process. Our extensive benchmarking results demonstrate that the proposed Uni-Mol+ significantly improves the accuracy of QC property prediction in various datasets. We have made the code and model publicly available at https://github.com/dptech-corp/Uni-Mol.

Molecular function is largely determined by structure. Accurately aligning molecular structure with natural language is therefore essential for enabling large language models (LLMs) to reason about downstream chemical tasks. However, the substantial cost of human annotation makes it infeasible to construct large-scale, high-quality datasets of structure-grounded descriptions. In this work, we propose a fully automated annotation framework for generating precise molecular structure descriptions at scale. Our approach builds upon and extends a rule-based chemical nomenclature parser to interpret IUPAC names and construct enriched, structured XML metadata that explicitly encodes molecular structure. This metadata is then used to guide LLMs in producing accurate natural-language descriptions. Using this framework, we curate a large-scale dataset of approximately 163k molecule-description pairs. A rigorous validation protocol combining LLM-based and expert human evaluation on a subset of 2,000 molecules demonstrates a high description precision of 98.6%. The resulting dataset provides a reliable foundation for future molecule-language alignment, and the proposed annotation method is readily extensible to larger datasets and broader chemical tasks that rely on structural descriptions.

Nuclear Magnetic Resonance (NMR) spectroscopy is the cornerstone of small-molecule structure elucidation. While deep learning has demonstrated significant potential in automating structure elucidation and spectral simulation, current progress is severely impeded by the reliance on synthetic datasets, which introduces significant domain shifts when applied to real-world experimental spectra. Furthermore, the lack of standardized evaluation protocols and rigorous data splitting strategies frequently leads to unfair comparisons and data leakage. To address these challenges, we introduce NMRGym, the largest and most comprehensive standardized dataset and benchmark derived from high-quality experimental NMR data to date. Comprising 269,999 unique molecules paired with high-fidelity ^1H and ^{13}C spectra, NMRGym bridges the critical gap between synthetic approximations and real-world diversity. We implement a strict quality control pipeline and unify data formats to ensure fair comparison. To strictly prevent data leakage, we enforce a scaffold-based split. Additionally, we provide fine-grained peak-atom level annotations to support future usage. Leveraging this resource, we establish a comprehensive evaluation suite covering diverse downstream tasks, including structure elucidation, functional group prediction from NMR, toxicity prediction from NMR, and spectral simulation, benchmarking representative state-of-the-art methodologies. Finally, we release an open-source leadboard with an automated leaderboard to foster community collaboration and standardize future research. The dataset, benchmark and leaderboard are publicly available at blue{https://AIMS-Lab-HKUSTGZ.github.io/NMRGym/}.

Optical Chemical Structure Recognition (OCSR) is crucial for digitizing chemical knowledge by converting molecular images into machine-readable formats. While recent vision-language models (VLMs) have shown potential in this task, their image-captioning approach often struggles with complex molecular structures and inconsistent annotations. To overcome these challenges, we introduce GTR-Mol-VLM, a novel framework featuring two key innovations: (1) the Graph Traversal as Visual Chain of Thought mechanism that emulates human reasoning by incrementally parsing molecular graphs through sequential atom-bond predictions, and (2) the data-centric principle of Faithfully Recognize What You've Seen, which addresses the mismatch between abbreviated structures in images and their expanded annotations. To support model development, we constructed GTR-CoT-1.3M, a large-scale instruction-tuning dataset with meticulously corrected annotations, and introduced MolRec-Bench, the first benchmark designed for a fine-grained evaluation of graph-parsing accuracy in OCSR. Comprehensive experiments demonstrate that GTR-Mol-VLM achieves superior results compared to specialist models, chemistry-domain VLMs, and commercial general-purpose VLMs. Notably, in scenarios involving molecular images with functional group abbreviations, GTR-Mol-VLM outperforms the second-best baseline by approximately 14 percentage points, both in SMILES-based and graph-based metrics. We hope that this work will drive OCSR technology to more effectively meet real-world needs, thereby advancing the fields of cheminformatics and AI for Science. We will release GTR-CoT at https://github.com/opendatalab/GTR-CoT.

Machine learning force fields (MLFF) have been proposed to accelerate molecular dynamics (MD) simulation, which finds widespread applications in chemistry and biomedical research. Even for the most data-efficient MLFFs, reaching chemical accuracy can require hundreds of frames of force and energy labels generated by expensive quantum mechanical algorithms, which may scale as O(n^3) to O(n^7), with n proportional to the number of basis functions. To address this issue, we propose a multi-stage computational framework -- ASTEROID, which lowers the data cost of MLFFs by leveraging a combination of cheap inaccurate data and expensive accurate data. The motivation behind ASTEROID is that inaccurate data, though incurring large bias, can help capture the sophisticated structures of the underlying force field. Therefore, we first train a MLFF model on a large amount of inaccurate training data, employing a bias-aware loss function to prevent the model from overfitting tahe potential bias of this data. We then fine-tune the obtained model using a small amount of accurate training data, which preserves the knowledge learned from the inaccurate training data while significantly improving the model's accuracy. Moreover, we propose a variant of ASTEROID based on score matching for the setting where the inaccurate training data are unlabeled. Extensive experiments on MD datasets and downstream tasks validate the efficacy of ASTEROID. Our code and data are available at https://github.com/abukharin3/asteroid.

The discovery of next-generation photoinitiators for two-photon polymerization (TPP) is hindered by the absence of large, open datasets containing the quantum-chemical and photophysical properties required to model photodissociation and excited-state behavior. Existing molecular datasets typically provide only basic physicochemical descriptors and therefore cannot support data-driven screening or AI-assisted design of photoinitiators. To address this gap, we introduce QuantumChem-200K, a large-scale dataset of over 200,000 organic molecules annotated with eleven quantum-chemical properties, including two-photon absorption (TPA) cross sections, TPA spectral ranges, singlet-triplet intersystem crossing (ISC) energies, toxicity and synthetic accessibility scores, hydrophilicity, solubility, boiling point, molecular weight, and aromaticity. These values are computed using a hybrid workflow that integrates density function theory (DFT), semi-empirical excited-state methods, atomistic quantum solvers, and neural-network predictors. Using QuantumChem-200K, we fine tune the open-source Qwen2.5-32B large language model to create a chemistry AI assistant capable of forward property prediction from SMILES. Benchmarking on 3000 unseen molecules from VQM24 and ZINC20 demonstrates that domain-specific fine-tuning significantly improves accuracy over GPT-4o, Llama-3.1-70B, and the base Qwen2.5-32B model, particularly for TPA and ISC predictions central to photoinitiator design. QuantumChem-200K and the corresponding AI assistant together provide the first scalable platform for high-throughput, LLM-driven photoinitiator screening and accelerated discovery of photosensitive materials.

Chemical reasoning usually involves complex, multi-step processes that demand precise calculations, where even minor errors can lead to cascading failures. Furthermore, large language models (LLMs) encounter difficulties handling domain-specific formulas, executing reasoning steps accurately, and integrating code effectively when tackling chemical reasoning tasks. To address these challenges, we present ChemAgent, a novel framework designed to improve the performance of LLMs through a dynamic, self-updating library. This library is developed by decomposing chemical tasks into sub-tasks and compiling these sub-tasks into a structured collection that can be referenced for future queries. Then, when presented with a new problem, ChemAgent retrieves and refines pertinent information from the library, which we call memory, facilitating effective task decomposition and the generation of solutions. Our method designs three types of memory and a library-enhanced reasoning component, enabling LLMs to improve over time through experience. Experimental results on four chemical reasoning datasets from SciBench demonstrate that ChemAgent achieves performance gains of up to 46% (GPT-4), significantly outperforming existing methods. Our findings suggest substantial potential for future applications, including tasks such as drug discovery and materials science. Our code can be found at https://github.com/gersteinlab/chemagent

Machine learning potentials (MLPs) trained on accurate quantum chemical data can retain the high accuracy, while inflicting little computational demands. On the downside, they need to be trained for each individual system. In recent years, a vast number of MLPs has been trained from scratch because learning additional data typically requires to train again on all data to not forget previously acquired knowledge. Additionally, most common structural descriptors of MLPs cannot represent efficiently a large number of different chemical elements. In this work, we tackle these problems by introducing element-embracing atom-centered symmetry functions (eeACSFs) which combine structural properties and element information from the periodic table. These eeACSFs are a key for our development of a lifelong machine learning potential (lMLP). Uncertainty quantification can be exploited to transgress a fixed, pre-trained MLP to arrive at a continuously adapting lMLP, because a predefined level of accuracy can be ensured. To extend the applicability of an lMLP to new systems, we apply continual learning strategies to enable autonomous and on-the-fly training on a continuous stream of new data. For the training of deep neural networks, we propose the continual resilient (CoRe) optimizer and incremental learning strategies relying on rehearsal of data, regularization of parameters, and the architecture of the model.

Advancements in neural machinery have led to a wide range of algorithmic solutions for molecular property prediction. Two classes of models in particular have yielded promising results: neural networks applied to computed molecular fingerprints or expert-crafted descriptors, and graph convolutional neural networks that construct a learned molecular representation by operating on the graph structure of the molecule. However, recent literature has yet to clearly determine which of these two methods is superior when generalizing to new chemical space. Furthermore, prior research has rarely examined these new models in industry research settings in comparison to existing employed models. In this paper, we benchmark models extensively on 19 public and 16 proprietary industrial datasets spanning a wide variety of chemical endpoints. In addition, we introduce a graph convolutional model that consistently matches or outperforms models using fixed molecular descriptors as well as previous graph neural architectures on both public and proprietary datasets. Our empirical findings indicate that while approaches based on these representations have yet to reach the level of experimental reproducibility, our proposed model nevertheless offers significant improvements over models currently used in industrial workflows.

Computational high-throughput virtual screening is essential for identifying redox-active molecules for sustainable applications such as electrochemical carbon capture. A primary challenge in this approach is the high computational cost associated with accurate quantum chemistry calculations. Machine learning foundation potentials (FPs) trained on extensive density functional theory (DFT) calculations offer a computationally efficient alternative. Here, we benchmark the MACE-OMol-0 and UMA FPs against a hierarchy of DFT functionals for predicting experimental molecular redox potentials for both electron transfer (ET) and proton-coupled electron transfer (PCET) reactions. We find that these FPs achieve exceptional accuracy for PCET processes, rivaling their target DFT method. However, the performance is diminished for ET reactions, particularly for multi-electron transfers involving reactive ions that are underrepresented in the OMol25 training data, revealing a key out-of-distribution limitation. To overcome this, we propose an optimal hybrid workflow that uses the FPs for efficient geometry optimization and thermochemical analysis, followed by a crucial single-point DFT energy refinement and an implicit solvation correction. This pragmatic approach provides a robust and scalable strategy for accelerating high-throughput virtual screening in sustainable chemistry.

Foundation models have been transformational in machine learning fields such as natural language processing and computer vision. Similar success in atomic property prediction has been limited due to the challenges of training effective models across multiple chemical domains. To address this, we introduce Joint Multi-domain Pre-training (JMP), a supervised pre-training strategy that simultaneously trains on multiple datasets from different chemical domains, treating each dataset as a unique pre-training task within a multi-task framework. Our combined training dataset consists of sim120M systems from OC20, OC22, ANI-1x, and Transition-1x. We evaluate performance and generalization by fine-tuning over a diverse set of downstream tasks and datasets including: QM9, rMD17, MatBench, QMOF, SPICE, and MD22. JMP demonstrates an average improvement of 59% over training from scratch, and matches or sets state-of-the-art on 34 out of 40 tasks. Our work highlights the potential of pre-training strategies that utilize diverse data to advance property prediction across chemical domains, especially for low-data tasks.

The overwhelming majority of molecules remains unexplored. This is mostly due to the sheer number of them, which prohibits any enumeration of chemical space, the set of all such molecules. In practice, only subsets of chemical space are considered, but those subsets exhibit substantial bias, prohibiting data-driven characterization of chemical space itself. In this work, we provide a method produce unbiased representative random samples of chemical space without enumeration of constituent molecules and to estimate the number of molecules in any custom chemical space. The approach is applicable to molecules which can be represented as graph and runs efficiently even for molecules of 30 atoms. We use it to estimate the representativeness of current databases with respect to their underlying chemical space and to establish a necessary criterion for a lower bound of database sizes to be representative of an underlying chemical space.

Molecule generation is advancing rapidly in chemical discovery and drug design. Flow matching methods have recently set the state of the art (SOTA) in unconditional molecule generation, surpassing score-based diffusion models. However, diffusion models still lead in property-guided generation. In this work, we introduce PropMolFlow, a novel approach for property-guided molecule generation based on geometry-complete SE(3)-equivariant flow matching. Integrating five different property embedding methods with a Gaussian expansion of scalar properties, PropMolFlow outperforms previous SOTA diffusion models in conditional molecule generation across various properties while preserving the stability and validity of the generated molecules, consistent with its unconditional counterpart. Additionally, it enables faster inference with significantly fewer time steps compared to baseline models. We highlight the importance of validating the properties of generated molecules through DFT calculations performed at the same level of theory as the training data. Specifically, our analysis identifies properties that require DFT validation and others where a pretrained SE(3) geometric vector perceptron regressors provide sufficiently accurate predictions on generated molecules. Furthermore, we introduce a new property metric designed to assess the model's ability to propose molecules with underrepresented property values, assessing its capacity for out-of-distribution generalization. Our findings reveal shortcomings in existing structural metrics, which mistakenly validate open-shell molecules or molecules with invalid valence-charge configurations, underscoring the need for improved evaluation frameworks. Overall, this work paves the way for developing targeted property-guided generation methods, enhancing the design of molecular generative models for diverse applications.

Obtaining the desired effect of drugs is highly dependent on their molecular geometries. Thus, the current prevailing paradigm focuses on 3D point-cloud atom representations, utilizing graph neural network (GNN) parametrizations, with rotational symmetries baked in via E(3) invariant layers. We prove that such models must necessarily disregard chirality, a geometric property of the molecules that cannot be superimposed on their mirror image by rotation and translation. Chirality plays a key role in determining drug safety and potency. To address this glaring issue, we introduce a novel field-based representation, proposing reference rotations that replace rotational symmetry constraints. The proposed model captures all molecular geometries including chirality, while still achieving highly competitive performance with E(3)-based methods across standard benchmarking metrics.

The advent of material databases provides an unprecedented opportunity to uncover predictive descriptors for emergent material properties from vast data space. However, common reliance on high-throughput ab initio data necessarily inherits limitations of such data: mismatch with experiments. On the other hand, experimental decisions are often guided by an expert's intuition honed from experiences that are rarely articulated. We propose using machine learning to "bottle" such operational intuition into quantifiable descriptors using expertly curated measurement-based data. We introduce "Materials Expert-Artificial Intelligence" (ME-AI) to encapsulate and articulate this human intuition. As a first step towards such a program, we focus on the topological semimetal (TSM) among square-net materials as the property inspired by the expert-identified descriptor based on structural information: the tolerance factor. We start by curating a dataset encompassing 12 primary features of 879 square-net materials, using experimental data whenever possible. We then use Dirichlet-based Gaussian process regression using a specialized kernel to reveal composite descriptors for square-net topological semimetals. The ME-AI learned descriptors independently reproduce expert intuition and expand upon it. Specifically, new descriptors point to hypervalency as a critical chemical feature predicting TSM within square-net compounds. Our success with a carefully defined problem points to the "machine bottling human insight" approach as promising for machine learning-aided material discovery.

Graph neural networks are emerging as promising methods for modeling molecular graphs, in which nodes and edges correspond to atoms and chemical bonds, respectively. Recent studies show that when 3D molecular geometries, such as bond lengths and angles, are available, molecular property prediction tasks can be made more accurate. However, computing of 3D molecular geometries requires quantum calculations that are computationally prohibitive. For example, accurate calculation of 3D geometries of a small molecule requires hours of computing time using density functional theory (DFT). Here, we propose to predict the ground-state 3D geometries from molecular graphs using machine learning methods. To make this feasible, we develop a benchmark, known as Molecule3D, that includes a dataset with precise ground-state geometries of approximately 4 million molecules derived from DFT. We also provide a set of software tools for data processing, splitting, training, and evaluation, etc. Specifically, we propose to assess the error and validity of predicted geometries using four metrics. We implement two baseline methods that either predict the pairwise distance between atoms or atom coordinates in 3D space. Experimental results show that, compared with generating 3D geometries with RDKit, our method can achieve comparable prediction accuracy but with much smaller computational costs. Our Molecule3D is available as a module of the MoleculeX software library (https://github.com/divelab/MoleculeX).

Lack of rigorous reproducibility and validation are major hurdles for scientific development across many fields. Materials science in particular encompasses a variety of experimental and theoretical approaches that require careful benchmarking. Leaderboard efforts have been developed previously to mitigate these issues. However, a comprehensive comparison and benchmarking on an integrated platform with multiple data modalities with both perfect and defect materials data is still lacking. This work introduces JARVIS-Leaderboard, an open-source and community-driven platform that facilitates benchmarking and enhances reproducibility. The platform allows users to set up benchmarks with custom tasks and enables contributions in the form of dataset, code, and meta-data submissions. We cover the following materials design categories: Artificial Intelligence (AI), Electronic Structure (ES), Force-fields (FF), Quantum Computation (QC) and Experiments (EXP). For AI, we cover several types of input data, including atomic structures, atomistic images, spectra, and text. For ES, we consider multiple ES approaches, software packages, pseudopotentials, materials, and properties, comparing results to experiment. For FF, we compare multiple approaches for material property predictions. For QC, we benchmark Hamiltonian simulations using various quantum algorithms and circuits. Finally, for experiments, we use the inter-laboratory approach to establish benchmarks. There are 1281 contributions to 274 benchmarks using 152 methods with more than 8 million data-points, and the leaderboard is continuously expanding. The JARVIS-Leaderboard is available at the website: https://pages.nist.gov/jarvis_leaderboard

Methods of computational quantum chemistry provide accurate approximations of molecular properties crucial for computer-aided drug discovery and other areas of chemical science. However, high computational complexity limits the scalability of their applications. Neural network potentials (NNPs) are a promising alternative to quantum chemistry methods, but they require large and diverse datasets for training. This work presents a new dataset and benchmark called nabla^2DFT that is based on the nablaDFT. It contains twice as much molecular structures, three times more conformations, new data types and tasks, and state-of-the-art models. The dataset includes energies, forces, 17 molecular properties, Hamiltonian and overlap matrices, and a wavefunction object. All calculations were performed at the DFT level (omegaB97X-D/def2-SVP) for each conformation. Moreover, nabla^2DFT is the first dataset that contains relaxation trajectories for a substantial number of drug-like molecules. We also introduce a novel benchmark for evaluating NNPs in molecular property prediction, Hamiltonian prediction, and conformational optimization tasks. Finally, we propose an extendable framework for training NNPs and implement 10 models within it.

The automatic analysis of chemical literature has immense potential to accelerate the discovery of new materials and drugs. Much of the critical information in patent documents and scientific articles is contained in figures, depicting the molecule structures. However, automatically parsing the exact chemical structure is a formidable challenge, due to the amount of detailed information, the diversity of drawing styles, and the need for training data. In this work, we introduce MolGrapher to recognize chemical structures visually. First, a deep keypoint detector detects the atoms. Second, we treat all candidate atoms and bonds as nodes and put them in a graph. This construct allows a natural graph representation of the molecule. Last, we classify atom and bond nodes in the graph with a Graph Neural Network. To address the lack of real training data, we propose a synthetic data generation pipeline producing diverse and realistic results. In addition, we introduce a large-scale benchmark of annotated real molecule images, USPTO-30K, to spur research on this critical topic. Extensive experiments on five datasets show that our approach significantly outperforms classical and learning-based methods in most settings. Code, models, and datasets are available.

The large and chemically diverse GMTKN55 benchmark was used as a training set for parametrizing composite wave function thermochemistry protocols akin to G4(MP2)XK theory (Chan et al, JCTC 2019, 15, 4478-4484). Even after reparametrization, the GMTKN55 WTMAD2 (weighted mean absolute deviation, type 2) for G4(MP2)-XK is actually inferior to that of the best rung-4 DFT functional, wB97M-V. By increasing the basis set for the MP2 part to def2-QZVPPD, we were able to substantially improve performance at modest cost (if an RI-MP2 approximation is made), with WTMAD2 for this G4(MP2)-XK-D method now comparable to the better rung-5 functionals (albeit at greater cost). A three-tier approach with a scaled MP3/def2-TZVPP intermediate step, however, leads to a G4(MP3)-D method that is markedly superior to even the best double hybrids wB97M(2) and revDSD-PBEP86-D4. Evaluating the CCSD(T) component with a triple-zeta, rather than split-valence, basis set yields only a modest further improvement that is incommensurate with the drastic increase in computational cost. G4(MP3)-D and G4(MP2)- XK-D have about 40% better WTMAD2, at similar or lower computational cost, than their counterparts G4 and G4(MP2), respectively: detailed comparison reveals that the difference lies in larger molecules due to basis set incompleteness error. An E2/ {T,Q} extrapolation and a CCSD(T)/def2-TZVP step provided the G4-T method of high accuracy and with just three fitted parameters. Using KS orbitals in MP2 leads to the G4(MP3|KS)-D method, which entirely eliminates the CCSD(T) step and has no steps costlier than scaled MP3; this shows a path forward to further improvements in double-hybrid density functional methods. G4-T-DLPNO, a variant in which post-MP2 corrections are evaluated at the DLPNO- CCSD(T) level, achieves nearly the accuracy of G4-T but is applicable to much larger systems.

The task of locating first order saddle points on high-dimensional surfaces describing the variation of energy as a function of atomic coordinates is an essential step for identifying the mechanism and estimating the rate of thermally activated events within the harmonic approximation of transition state theory. When combined directly with electronic structure calculations, the number of energy and atomic force evaluations needed for convergence is a primary issue. Here, we describe an efficient implementation of Gaussian process regression (GPR) acceleration of the minimum mode following method where a dimer is used to estimate the lowest eigenmode of the Hessian. A surrogate energy surface is constructed and updated after each electronic structure calculation. The method is applied to a test set of 500 molecular reactions previously generated by Hermez and coworkers [J. Chem. Theory Comput. 18, 6974 (2022)]. An order of magnitude reduction in the number of electronic structure calculations needed to reach the saddle point configurations is obtained by using the GPR compared to the dimer method. Despite the wide range in stiffness of the molecular degrees of freedom, the calculations are carried out using Cartesian coordinates and are found to require similar number of electronic structure calculations as an elaborate internal coordinate method implemented in the Sella software package. The present implementation of the GPR surrogate model in C++ is efficient enough for the wall time of the saddle point searches to be reduced in 3 out of 4 cases even though the calculations are carried out at a low Hartree-Fock level.

Supervised machine learning approaches have been increasingly used in accelerating electronic structure prediction as surrogates of first-principle computational methods, such as density functional theory (DFT). While numerous quantum chemistry datasets focus on chemical properties and atomic forces, the ability to achieve accurate and efficient prediction of the Hamiltonian matrix is highly desired, as it is the most important and fundamental physical quantity that determines the quantum states of physical systems and chemical properties. In this work, we generate a new Quantum Hamiltonian dataset, named as QH9, to provide precise Hamiltonian matrices for 999 or 2998 molecular dynamics trajectories and 130,831 stable molecular geometries, based on the QM9 dataset. By designing benchmark tasks with various molecules, we show that current machine learning models have the capacity to predict Hamiltonian matrices for arbitrary molecules. Both the QH9 dataset and the baseline models are provided to the community through an open-source benchmark, which can be highly valuable for developing machine learning methods and accelerating molecular and materials design for scientific and technological applications. Our benchmark is publicly available at https://github.com/divelab/AIRS/tree/main/OpenDFT/QHBench.

Large-scale pre-training methodologies for chemical language models represent a breakthrough in cheminformatics. These methods excel in tasks such as property prediction and molecule generation by learning contextualized representations of input tokens through self-supervised learning on large unlabeled corpora. Typically, this involves pre-training on unlabeled data followed by fine-tuning on specific tasks, reducing dependence on annotated datasets and broadening chemical language representation understanding. This paper introduces a large encoder-decoder chemical foundation models pre-trained on a curated dataset of 91 million SMILES samples sourced from PubChem, which is equivalent to 4 billion of molecular tokens. The proposed foundation model supports different complex tasks, including quantum property prediction, and offer flexibility with two main variants (289M and 8times289M). Our experiments across multiple benchmark datasets validate the capacity of the proposed model in providing state-of-the-art results for different tasks. We also provide a preliminary assessment of the compositionality of the embedding space as a prerequisite for the reasoning tasks. We demonstrate that the produced latent space is separable compared to the state-of-the-art with few-shot learning capabilities.

The development of reliable and extensible molecular mechanics (MM) force fields -- fast, empirical models characterizing the potential energy surface of molecular systems -- is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods. Trained in a single GPU-day to fit a large and diverse quantum chemical dataset of over 1.1M energy and force calculations, espaloma-0.3 reproduces quantum chemical energetic properties of chemical domains highly relevant to drug discovery, including small molecules, peptides, and nucleic acids. Moreover, this force field maintains the quantum chemical energy-minimized geometries of small molecules and preserves the condensed phase properties of peptides, self-consistently parametrizing proteins and ligands to produce stable simulations leading to highly accurate predictions of binding free energies. This methodology demonstrates significant promise as a path forward for systematically building more accurate force fields that are easily extensible to new chemical domains of interest.

The development of accurate and efficient machine learning models for predicting the structure and properties of molecular crystals has been hindered by the scarcity of publicly available datasets of structures with property labels. To address this challenge, we introduce the Open Molecular Crystals 2025 (OMC25) dataset, a collection of over 27 million molecular crystal structures containing 12 elements and up to 300 atoms in the unit cell. The dataset was generated from dispersion-inclusive density functional theory (DFT) relaxation trajectories of over 230,000 randomly generated molecular crystal structures of around 50,000 organic molecules. OMC25 comprises diverse chemical compounds capable of forming different intermolecular interactions and a wide range of crystal packing motifs. We provide detailed information on the dataset's construction, composition, structure, and properties. To demonstrate the quality and use cases of OMC25, we further trained and evaluated state-of-the-art open-source machine learning interatomic potentials. By making this dataset publicly available, we aim to accelerate the development of more accurate and efficient machine learning models for molecular crystals.

Retrosynthesis planning poses a formidable challenge in the organic chemical industry, particularly in pharmaceuticals. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency. This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, Our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods. Scientific contribution: We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5\% (top-5) and 5.4\% (top-10) increased accuracy over the strongest baseline.

Density functional theory (DFT) stands as a cornerstone method in computational quantum chemistry and materials science due to its remarkable versatility and scalability. Yet, it suffers from limitations in accuracy, particularly when dealing with strongly correlated systems. To address these shortcomings, recent work has begun to explore how machine learning can expand the capabilities of DFT; an endeavor with many open questions and technical challenges. In this work, we present Grad DFT: a fully differentiable JAX-based DFT library, enabling quick prototyping and experimentation with machine learning-enhanced exchange-correlation energy functionals. Grad DFT employs a pioneering parametrization of exchange-correlation functionals constructed using a weighted sum of energy densities, where the weights are determined using neural networks. Moreover, Grad DFT encompasses a comprehensive suite of auxiliary functions, notably featuring a just-in-time compilable and fully differentiable self-consistent iterative procedure. To support training and benchmarking efforts, we additionally compile a curated dataset of experimental dissociation energies of dimers, half of which contain transition metal atoms characterized by strong electronic correlations. The software library is tested against experimental results to study the generalization capabilities of a neural functional across potential energy surfaces and atomic species, as well as the effect of training data noise on the resulting model accuracy.

Parameterized tight-binding models fit to first principles calculations can provide an efficient and accurate quantum mechanical method for predicting properties of molecules and solids. However, well-tested parameter sets are generally only available for a limited number of atom combinations, making routine use of this method difficult. Furthermore, most previous models consider only simple two-body interactions, which limits accuracy. To tackle these challenges, we develop a density functional theory database of nearly one million materials, which we use to fit a universal set of tight-binding parameters for 65 elements and their binary combinations. We include both two-body and three-body effective interaction terms in our model, plus self-consistent charge transfer, enabling our model to work for metallic, covalent, and ionic bonds with the same parameter set. To ensure predictive power, we adopt a learning framework where we repeatedly test the model on new low energy crystal structures and then add them to the fitting dataset, iterating until predictions improve. We distribute the materials database and tools developed in this work publicly.

Accurately classifying chemical structures is essential for cheminformatics and bioinformatics, including tasks such as identifying bioactive compounds of interest, screening molecules for toxicity to humans, finding non-organic compounds with desirable material properties, or organizing large chemical libraries for drug discovery or environmental monitoring. However, manual classification is labor-intensive and difficult to scale to large chemical databases. Existing automated approaches either rely on manually constructed classification rules, or the use of deep learning methods that lack explainability. This work presents an approach that uses generative artificial intelligence to automatically write chemical classifier programs for classes in the Chemical Entities of Biological Interest (ChEBI) database. These programs can be used for efficient deterministic run-time classification of SMILES structures, with natural language explanations. The programs themselves constitute an explainable computable ontological model of chemical class nomenclature, which we call the ChEBI Chemical Class Program Ontology (C3PO). We validated our approach against the ChEBI database, and compared our results against state of the art deep learning models. We also demonstrate the use of C3PO to classify out-of-distribution examples taken from metabolomics repositories and natural product databases. We also demonstrate the potential use of our approach to find systematic classification errors in existing chemical databases, and show how an ensemble artificial intelligence approach combining generated ontologies, automated literature search, and multimodal vision models can be used to pinpoint potential errors requiring expert validation

The efficient exploration of chemical space to design molecules with intended properties enables the accelerated discovery of drugs, materials, and catalysts, and is one of the most important outstanding challenges in chemistry. Encouraged by the recent surge in computer power and artificial intelligence development, many algorithms have been developed to tackle this problem. However, despite the emergence of many new approaches in recent years, comparatively little progress has been made in developing realistic benchmarks that reflect the complexity of molecular design for real-world applications. In this work, we develop a set of practical benchmark tasks relying on physical simulation of molecular systems mimicking real-life molecular design problems for materials, drugs, and chemical reactions. Additionally, we demonstrate the utility and ease of use of our new benchmark set by demonstrating how to compare the performance of several well-established families of algorithms. Surprisingly, we find that model performance can strongly depend on the benchmark domain. We believe that our benchmark suite will help move the field towards more realistic molecular design benchmarks, and move the development of inverse molecular design algorithms closer to designing molecules that solve existing problems in both academia and industry alike.

We introduce AceFF, a pre-trained machine learning interatomic potential (MLIP) optimized for small molecule drug discovery. While MLIPs have emerged as efficient alternatives to Density Functional Theory (DFT), generalizability across diverse chemical spaces remains difficult. AceFF addresses this via a refined TensorNet2 architecture trained on a comprehensive dataset of drug-like compounds. This approach yields a force field that balances high-throughput inference speed with DFT-level accuracy. AceFF fully supports the essential medicinal chemistry elements (H, B, C, N, O, F, Si, P, S, Cl, Br, I) and is explicitly trained to handle charged states. Validation against rigorous benchmarks, including complex torsional energy scans, molecular dynamics trajectories, batched minimizations, and forces and anergy accuracy demonstrates that AceFF establishes a new state-of-the-art for organic molecules. The AceFF-2 model weights and inference code are available at https://huggingface.co/Acellera/AceFF-2.0.

We present a vector-based method to balance chemical reactions. The algorithm builds candidates in a deterministic way, removes duplicates, and always prints coefficients in the lowest whole-number form. For redox cases, electrons and protons/hydroxide are treated explicitly, so both mass and charge are balanced. We also outline the basic principles of the vector formulation of stoichiometry, interpreting reactions as integer vectors in composition space, this geometric view supports compact visualizations of reagent-product interactions and helps surface distinct reaction families. The method enumerates valid balances for arbitrary user-specified species lists without special-case balancing rules or symbolic tricks, and it provides a clean foundation for developing new algorithmic variants (e.g., alternative objectives or constraints). On representative examples (neutralization, double displacement, decomposition, classical redox, small multicomponent sets) and a negative control, the method produced correct integer balances. When multiple balances exist, we report a canonical one - minimizing the total coefficient sum with a simple tie-breaker - without claiming global optimality beyond the solutions the search enumerates. The procedure applies per reaction and extends to reaction networks via consistent per-reaction application. We do not report runtimes, broader benchmarking and code/data release are planned.

Large language models (LLMs) have gained significant attention in chemistry. However, most existing datasets center on molecular-level property prediction and overlook the role of fine-grained functional group (FG) information. Incorporating FG-level data can provide valuable prior knowledge that links molecular structures with textual descriptions, which can be used to build more interpretable, structure-aware LLMs for reasoning on molecule-related tasks. Moreover, LLMs can learn from such fine-grained information to uncover hidden relationships between specific functional groups and molecular properties, thereby advancing molecular design and drug discovery. Here, we introduce FGBench, a dataset comprising 625K molecular property reasoning problems with functional group information. Functional groups are precisely annotated and localized within the molecule, which ensures the dataset's interoperability thereby facilitating further multimodal applications. FGBench includes both regression and classification tasks on 245 different functional groups across three categories for molecular property reasoning: (1) single functional group impacts, (2) multiple functional group interactions, and (3) direct molecular comparisons. In the benchmark of state-of-the-art LLMs on 7K curated data, the results indicate that current LLMs struggle with FG-level property reasoning, highlighting the need to enhance reasoning capabilities in LLMs for chemistry tasks. We anticipate that the methodology employed in FGBench to construct datasets with functional group-level information will serve as a foundational framework for generating new question-answer pairs, enabling LLMs to better understand fine-grained molecular structure-property relationships. The dataset and evaluation code are available at https://github.com/xuanliugit/FGBench.

Chemical representation learning has gained increasing interest due to the limited availability of supervised data in fields such as drug and materials design. This interest particularly extends to chemical language representation learning, which involves pre-training Transformers on SMILES sequences -- textual descriptors of molecules. Despite its success in molecular property prediction, current practices often lead to overfitting and limited scalability due to early convergence. In this paper, we introduce a novel chemical language representation learning framework, called MolTRES, to address these issues. MolTRES incorporates generator-discriminator training, allowing the model to learn from more challenging examples that require structural understanding. In addition, we enrich molecular representations by transferring knowledge from scientific literature by integrating external materials embedding. Experimental results show that our model outperforms existing state-of-the-art models on popular molecular property prediction tasks.

Self-supervised learning has recently gained growing interest in molecular modeling for scientific tasks such as AI-assisted drug discovery. Current studies consider leveraging both 2D and 3D molecular structures for representation learning. However, relying on straightforward alignment strategies that treat each modality separately, these methods fail to exploit the intrinsic correlation between 2D and 3D representations that reflect the underlying structural characteristics of molecules, and only perform coarse-grained molecule-level alignment. To derive fine-grained alignment and promote structural molecule understanding, we introduce an atomic-relation level "blend-then-predict" self-supervised learning approach, MoleBLEND, which first blends atom relations represented by different modalities into one unified relation matrix for joint encoding, then recovers modality-specific information for 2D and 3D structures individually. By treating atom relationships as anchors, MoleBLEND organically aligns and integrates visually dissimilar 2D and 3D modalities of the same molecule at fine-grained atomic level, painting a more comprehensive depiction of each molecule. Extensive experiments show that MoleBLEND achieves state-of-the-art performance across major 2D/3D molecular benchmarks. We further provide theoretical insights from the perspective of mutual-information maximization, demonstrating that our method unifies contrastive, generative (cross-modality prediction) and mask-then-predict (single-modality prediction) objectives into one single cohesive framework.

While Vision-Language Models (VLMs) have demonstrated significant potential in chemical visual understanding, current models are predominantly optimized for direct visual question-answering tasks. This paradigm often results in "black-box" systems that fail to utilize the inherent capability of Large Language Models (LLMs) to infer underlying reaction mechanisms. In this work, we introduce ChemVLR, a chemical VLM designed to prioritize reasoning within the perception process. Unlike conventional chemical VLMs, ChemVLR analyzes visual inputs in a fine-grained manner by explicitly identifying granular chemical descriptors, such as functional groups, prior to generating answers. This approach ensures the production of explicit and interpretable reasoning paths for complex visual chemical problems. To facilitate this methodology, we implement a cross-modality reverse-engineering strategy, combined with a rigorous filtering pipeline, to curate a large-scale reasoning-and-captioning dataset comprising 760k high-quality samples across molecular and reaction tasks. Furthermore, we adopt a three-stage training framework that systemically builds model perception and reasoning capacity. Experiments demonstrate that ChemVLR achieves state-of-the-art (SOTA) performance, surpassing both leading proprietary models and domain-specific open-source baselines. We also provide comprehensive ablation studies to validate our training strategy and data generation designs. Code and model weights will be available at https://github.com/xxlllz/ChemVLR.

Property prediction accuracy has long been a key parameter of machine learning in materials informatics. Accordingly, advanced models showing state-of-the-art performance turn into highly parameterized black boxes missing interpretability. Here, we present an elegant way to make their reasoning transparent. Human-readable text-based descriptions automatically generated within a suite of open-source tools are proposed as materials representation. Transformer language models pretrained on 2 million peer-reviewed articles take as input well-known terms, e.g., chemical composition, crystal symmetry, and site geometry. Our approach outperforms crystal graph networks by classifying four out of five analyzed properties if one considers all available reference data. Moreover, fine-tuned text-based models show high accuracy in the ultra-small data limit. Explanations of their internal machinery are produced using local interpretability techniques and are faithful and consistent with domain expert rationales. This language-centric framework makes accurate property predictions accessible to people without artificial-intelligence expertise.

The rapid expansion of chemistry literature poses significant challenges for researchers seeking to efficiently access domain-specific knowledge. To support advancements in chemistry-focused natural language processing (NLP), we present ChemRxivQuest, a curated dataset of 970 high-quality question-answer (QA) pairs derived from 155 ChemRxiv preprints across 17 subfields of chemistry. Each QA pair is explicitly linked to its source text segment to ensure traceability and contextual accuracy. ChemRxivQuest was constructed using an automated pipeline that combines optical character recognition (OCR), GPT-4o-based QA generation, and a fuzzy matching technique for answer verification. The dataset emphasizes conceptual, mechanistic, applied, and experimental questions, enabling applications in retrieval-based QA systems, search engine development, and fine-tuning of domain-adapted large language models. We analyze the dataset's structure, coverage, and limitations, and outline future directions for expansion and expert validation. ChemRxivQuest provides a foundational resource for chemistry NLP research, education, and tool development.

Retrosynthesis planning, essential in organic synthesis and drug discovery, has greatly benefited from recent AI-driven advancements. Nevertheless, existing methods frequently face limitations in both applicability and explainability. Traditional graph-based and sequence-to-sequence models often lack generalized chemical knowledge, leading to predictions that are neither consistently accurate nor easily explainable. To address these challenges, we introduce RetroDFM-R, a reasoning-based large language model (LLM) designed specifically for chemical retrosynthesis. Leveraging large-scale reinforcement learning guided by chemically verifiable rewards, RetroDFM-R significantly enhances prediction accuracy and explainability. Comprehensive evaluations demonstrate that RetroDFM-R significantly outperforms state-of-the-art methods, achieving a top-1 accuracy of 65.0% on the USPTO-50K benchmark. Double-blind human assessments further validate the chemical plausibility and practical utility of RetroDFM-R's predictions. RetroDFM-R also accurately predicts multistep retrosynthetic routes reported in the literature for both real-world drug molecules and perovskite materials. Crucially, the model's explicit reasoning process provides human-interpretable insights, thereby enhancing trust and practical value in real-world retrosynthesis applications.

Pretrained neural networks have attracted significant interest in chemistry and small molecule drug design. Embeddings from these models are widely used for molecular property prediction, virtual screening, and small data learning in molecular chemistry. This study presents the most extensive comparison of such models to date, evaluating 25 models across 25 datasets. Under a fair comparison framework, we assess models spanning various modalities, architectures, and pretraining strategies. Using a dedicated hierarchical Bayesian statistical testing model, we arrive at a surprising result: nearly all neural models show negligible or no improvement over the baseline ECFP molecular fingerprint. Only the CLAMP model, which is also based on molecular fingerprints, performs statistically significantly better than the alternatives. These findings raise concerns about the evaluation rigor in existing studies. We discuss potential causes, propose solutions, and offer practical recommendations.

The protein chemical shifts holds a large amount of information about the 3-dimensional structure of the protein. A number of chemical shift predictors based on the relationship between structures resolved with X-ray crystallography and the corresponding experimental chemical shifts have been developed. These empirical predictors are very accurate on X-ray structures but tends to be insensitive to small structural changes. To overcome this limitation it has been suggested to make chemical shift predictors based on quantum mechanical(QM) calculations. In this thesis the development of the QM derived chemical shift predictor Procs14 is presented. Procs14 is based on 2.35 million density functional theory(DFT) calculations on tripeptides and contains corrections for hydrogen bonding, ring current and the effect of the previous and following residue. Procs14 is capable at performing predictions for the 13CA, 13CB, 13CO, 15NH, 1HN and 1HA backbone atoms. In order to benchmark Procs14, a number of QM NMR calculations are performed on full protein structures. Of the tested empirical and QM derived predictors, Procs14 reproduced the QM chemical shifts with the highest accuracy. A comparison with the QM derived predictor CheShift-2 on X-ray structures and NMR ensembles with experimental chemical shift data, showed that Procs14 predicted the chemical shifts with the best accuracy. The predictions on the NMR ensembles exhibited the best performance. This suggests that future work might benefit from using ensemble sampling when performing simulations of protein folding with chemical shifts. Procs14 is implemented in the markov chain monte carlo protein folding framework PHAISTOS. The computational efficient implementation of Procs14 allows for rapid predictions and therefore potential use in refinement and folding of protein structures.

High-throughput reaction condition (RC) screening is fundamental to chemical synthesis. However, current RC screening suffers from laborious and costly trial-and-error workflows. Traditional computer-aided synthesis planning (CASP) tools fail to find suitable RCs due to data sparsity and inadequate reaction representations. Nowadays, large language models (LLMs) are capable of tackling chemistry-related problems, such as molecule design, and chemical logic Q\&A tasks. However, LLMs have not yet achieved accurate predictions of chemical reaction conditions. Here, we present MM-RCR, a text-augmented multimodal LLM that learns a unified reaction representation from SMILES, reaction graphs, and textual corpus for chemical reaction recommendation (RCR). To train MM-RCR, we construct 1.2 million pair-wised Q\&A instruction datasets. Our experimental results demonstrate that MM-RCR achieves state-of-the-art performance on two open benchmark datasets and exhibits strong generalization capabilities on out-of-domain (OOD) and High-Throughput Experimentation (HTE) datasets. MM-RCR has the potential to accelerate high-throughput condition screening in chemical synthesis.

Virtual Screening is an essential technique in the early phases of drug discovery, aimed at identifying promising drug candidates from vast molecular libraries. Recently, ligand-based virtual screening has garnered significant attention due to its efficacy in conducting extensive database screenings without relying on specific protein-binding site information. Obtaining binding affinity data for complexes is highly expensive, resulting in a limited amount of available data that covers a relatively small chemical space. Moreover, these datasets contain a significant amount of inconsistent noise. It is challenging to identify an inductive bias that consistently maintains the integrity of molecular activity during data augmentation. To tackle these challenges, we propose S-MolSearch, the first framework to our knowledge, that leverages molecular 3D information and affinity information in semi-supervised contrastive learning for ligand-based virtual screening. Drawing on the principles of inverse optimal transport, S-MolSearch efficiently processes both labeled and unlabeled data, training molecular structural encoders while generating soft labels for the unlabeled data. This design allows S-MolSearch to adaptively utilize unlabeled data within the learning process. Empirically, S-MolSearch demonstrates superior performance on widely-used benchmarks LIT-PCBA and DUD-E. It surpasses both structure-based and ligand-based virtual screening methods for AUROC, BEDROC and EF.

The reliability with Machine Learning (ML) techniques in novel materials discovery often depend on the quality of the dataset, in addition to the relevant features used in describing the material. In this regard, the current study presents and validates a newly processed materials dataset that can be utilized for benchmark ML analysis, as it relates to the prediction and classification of deterministic target properties. Originally, the dataset was extracted from the Open Quantum Materials Database (OQMD) and contains a robust 16,323 samples of ABX3 inorganic perovskite structures. The dataset is tabular in form and is preprocessed to include sixty-one generalized input features that broadly describes the physicochemical, stability/geometrical, and Density Functional Theory (DFT) target properties associated with the elemental ionic sites in a three-dimensional ABX3 polyhedral. For validation, four different ML models are employed to predict three distinctive target properties, namely: formation energy, energy band gap, and crystal system. On experimentation, the best accuracy measurements are reported at 0.013 eV/atom MAE, 0.216 eV MAE, and 85% F1, corresponding to the formation energy prediction, band gap prediction and crystal system multi-classification, respectively. Moreover, the realized results are compared with previous literature and as such, affirms the resourcefulness of the current dataset for future benchmark materials analysis via ML techniques. The preprocessed dataset and source codes are openly available to download from github.com/chenebuah/ML_abx3_dataset.

Catalysis at solid-liquid interfaces plays a central role in the advancement of energy storage and sustainable chemical production technologies. By enabling accurate, long-time scale simulations, machine learning (ML) models have the potential to accelerate the discovery of (electro)catalysts. While prior Open Catalyst datasets (OC20 and OC22) have advanced the field by providing large-scale density functional theory (DFT) data of adsorbates on surfaces at solid-gas interfaces, they do not capture the critical role of solvent and electrolyte effects at solid-liquid interfaces. To bridge this gap, we introduce the Open Catalyst 2025 (OC25) dataset, consisting of 7,801,261 calculations across 1,511,270 unique explicit solvent environments. OC25 constitutes the largest and most diverse solid-liquid interface dataset that is currently available and provides configurational and elemental diversity: spanning 88 elements, commonly used solvents/ions, varying solvent layers, and off-equilibrium sampling. State-of-the-art models trained on the OC25 dataset exhibit energy, force, and solvation energy errors as low as 0.1 eV, 0.015 eV/A, and 0.04 eV, respectively; significantly lower than than the recently released Universal Models for Atoms (UMA-OC20). Additionally, we discuss the impact of the quality of DFT-calculated forces on model training and performance. The dataset and accompanying baseline models are made openly available for the community. We anticipate the dataset to facilitate large length-scale and long-timescale simulations of catalytic transformations at solid-liquid interfaces, advancing molecular-level insights into functional interfaces and enabling the discovery of next-generation energy storage and conversion technologies.

In recent decades, chemistry publications and patents have increased rapidly. A significant portion of key information is embedded in molecular structure figures, complicating large-scale literature searches and limiting the application of large language models in fields such as biology, chemistry, and pharmaceuticals. The automatic extraction of precise chemical structures is of critical importance. However, the presence of numerous Markush structures in real-world documents, along with variations in molecular image quality, drawing styles, and noise, significantly limits the performance of existing optical chemical structure recognition (OCSR) methods. We present MolParser, a novel end-to-end OCSR method that efficiently and accurately recognizes chemical structures from real-world documents, including difficult Markush structure. We use a extended SMILES encoding rule to annotate our training dataset. Under this rule, we build MolParser-7M, the largest annotated molecular image dataset to our knowledge. While utilizing a large amount of synthetic data, we employed active learning methods to incorporate substantial in-the-wild data, specifically samples cropped from real patents and scientific literature, into the training process. We trained an end-to-end molecular image captioning model, MolParser, using a curriculum learning approach. MolParser significantly outperforms classical and learning-based methods across most scenarios, with potential for broader downstream applications. The dataset is publicly available.

GNNs and chemical fingerprints are the predominant approaches to representing molecules for property prediction. However, in NLP, transformers have become the de-facto standard for representation learning thanks to their strong downstream task transfer. In parallel, the software ecosystem around transformers is maturing rapidly, with libraries like HuggingFace and BertViz enabling streamlined training and introspection. In this work, we make one of the first attempts to systematically evaluate transformers on molecular property prediction tasks via our ChemBERTa model. ChemBERTa scales well with pretraining dataset size, offering competitive downstream performance on MoleculeNet and useful attention-based visualization modalities. Our results suggest that transformers offer a promising avenue of future work for molecular representation learning and property prediction. To facilitate these efforts, we release a curated dataset of 77M SMILES from PubChem suitable for large-scale self-supervised pretraining.

Molecular representations are inherently task-dependent, yet most pre-trained molecular encoders are not. Task conditioning promises representations that reorganize based on task descriptions, but existing approaches rely on expensive labeled data. We show that weak supervision on programmatically derived molecular motifs is sufficient. Our Adaptive Chemical Embedding Model (ACE-Mol) learns from hundreds of motifs paired with natural language descriptors that are cheap to compute, trivial to scale. Conventional encoders slowly search the embedding space for task-relevant structure, whereas ACE-Mol immediately aligns its representations with the task. ACE-Mol achieves state-of-the-art performance across molecular property prediction benchmarks with interpretable, chemically meaningful representations.

Molecular property prediction is crucial for drug discovery and materials science, yet existing approaches suffer from limited interpretability, poor cross-task generalization, and lack of chemical reasoning capabilities. Traditional machine learning models struggle with task transferability, while specialized molecular language models provide little insight into their decision-making processes. To address these limitations, we propose MPPReasoner, a multimodal large language model that incorporates chemical reasoning for molecular property prediction. Our approach, built upon Qwen2.5-VL-7B-Instruct, integrates molecular images with SMILES strings to enable comprehensive molecular understanding. We develop a two-stage training strategy: supervised fine-tuning (SFT) using 16,000 high-quality reasoning trajectories generated through expert knowledge and multiple teacher models, followed by Reinforcement Learning from Principle-Guided Rewards (RLPGR). RLPGR employs verifiable, rule-based rewards that systematically evaluate chemical principle application, molecular structure analysis, and logical consistency through computational verification. Extensive experiments across 8 datasets demonstrate significant performance improvements, with MPPReasoner outperforming the best baselines by 7.91\% and 4.53\% on in-distribution and out-of-distribution tasks respectively. MPPReasoner exhibits exceptional cross-task generalization and generates chemically sound reasoning paths that provide valuable insights into molecular property analysis, substantially enhancing both interpretability and practical utility for chemists. Code is available at https://anonymous.4open.science/r/MPPReasoner-12687.

Precise recognition, editing, and generation of molecules are essential prerequisites for both chemists and AI systems tackling various chemical tasks. We present MolLangBench, a comprehensive benchmark designed to evaluate fundamental molecule-language interface tasks: language-prompted molecular structure recognition, editing, and generation. To ensure high-quality, unambiguous, and deterministic outputs, we construct the recognition tasks using automated cheminformatics tools, and curate editing and generation tasks through rigorous expert annotation and validation. MolLangBench supports the evaluation of models that interface language with different molecular representations, including linear strings, molecular images, and molecular graphs. Evaluations of state-of-the-art models reveal significant limitations: the strongest model (o3) achieves 79.2% and 78.5% accuracy on recognition and editing tasks, which are intuitively simple for humans, and performs even worse on the generation task, reaching only 29.0% accuracy. These results highlight the shortcomings of current AI systems in handling even preliminary molecular recognition and manipulation tasks. We hope MolLangBench will catalyze further research toward more effective and reliable AI systems for chemical applications.

Foundation models have shown remarkable success across scientific domains, yet their impact in chemistry remains limited due to the absence of diverse, large-scale, high-quality datasets that reflect the field's multifaceted nature. We present the ChemPile, an open dataset containing over 75 billion tokens of curated chemical data, specifically built for training and evaluating general-purpose models in the chemical sciences. The dataset mirrors the human learning journey through chemistry -- from educational foundations to specialized expertise -- spanning multiple modalities and content types including structured data in diverse chemical representations (SMILES, SELFIES, IUPAC names, InChI, molecular renderings), scientific and educational text, executable code, and chemical images. ChemPile integrates foundational knowledge (textbooks, lecture notes), specialized expertise (scientific articles and language-interfaced data), visual understanding (molecular structures, diagrams), and advanced reasoning (problem-solving traces and code) -- mirroring how human chemists develop expertise through diverse learning materials and experiences. Constructed through hundreds of hours of expert curation, the ChemPile captures both foundational concepts and domain-specific complexity. We provide standardized training, validation, and test splits, enabling robust benchmarking. ChemPile is openly released via HuggingFace with a consistent API, permissive license, and detailed documentation. We hope the ChemPile will serve as a catalyst for chemical AI, enabling the development of the next generation of chemical foundation models.

Traditional AI methods often rely on task-specific model designs and training, which constrain both the scalability of model size and generalization across different tasks. Here, we introduce ChemFM, a large foundation model specifically developed for chemicals. By conducting a series of scaling experiments, we identify UniChem as the informative molecular database for pre-training the foundation model. ChemFM comprises 3 billion parameters and is pre-trained on 178 million molecules using self-supervised causal language modeling to extract generalizable molecular representations. This model can be adapted to diverse downstream chemical applications using either full-parameter or parameter-efficient fine-tuning methods. ChemFM consistently outperforms state-of-the-art task-specific AI models across all tested tasks. Notably, it achieves up to 67.48% performance improvement across 34 property prediction benchmarks, up to 33.80% reduction in mean average deviation between conditioned and actual properties of generated molecules in conditional molecular generation tasks, and up to 3.7% top-1 accuracy improvement across 4 reaction prediction datasets. Moreover, ChemFM demonstrates its superior performance in predicting antibiotic activity and cytotoxicity, highlighting its potential to advance the discovery of novel antibiotics. Furthermore, we demonstrate that, as a foundation model, ChemFM exhibits strong data efficiency, requiring significantly fewer labeled training samples to achieve state-of-the-art performance. We anticipate that ChemFM will significantly advance chemistry research by providing a foundation model capable of effectively generalizing across a broad range of tasks with minimal additional training.

Recent advances in large language models (LLMs) have led to models that tackle diverse molecular tasks, such as chemical reaction prediction and molecular property prediction. Large-scale molecular instruction-tuning datasets have enabled sequence-only (e.g., SMILES or SELFIES) generalist molecular LLMs, and researchers are now exploring multimodal approaches that incorporate molecular structural information for further gains. However, a genuinely multimodal, generalist LLM that covers a broad spectrum of molecular tasks has yet to be fully investigated. We observe that naive next token prediction training ignores graph-structural information, limiting an LLM's ability to exploit molecular graphs. To address this, we propose (i) Molecular structure Preference Optimization (MolPO), which facilitates graph usage by optimizing preferences between pairs of correct and perturbed molecular structures, and (ii) an advanced graph encoder with a tailored pre-training strategy to improve the effect of graph utilization by MolPO. Building on these contributions, we introduce Mol-LLM, the first multimodal generalist model that (a) handles a broad spectrum of molecular tasks among molecular LLMs, (b) explicitly leverages molecular-structure information, and (c) takes advantage of extensive instruction tuning. Mol-LLM attains state-of-the-art or comparable results across the most comprehensive molecular-LLM benchmark-even on out-of-distribution datasets for reaction and property prediction, where it surpasses prior generalist molecular LLMs by a large margin.

Supervised learning on molecules has incredible potential to be useful in chemistry, drug discovery, and materials science. Luckily, several promising and closely related neural network models invariant to molecular symmetries have already been described in the literature. These models learn a message passing algorithm and aggregation procedure to compute a function of their entire input graph. At this point, the next step is to find a particularly effective variant of this general approach and apply it to chemical prediction benchmarks until we either solve them or reach the limits of the approach. In this paper, we reformulate existing models into a single common framework we call Message Passing Neural Networks (MPNNs) and explore additional novel variations within this framework. Using MPNNs we demonstrate state of the art results on an important molecular property prediction benchmark; these results are strong enough that we believe future work should focus on datasets with larger molecules or more accurate ground truth labels.

Classical empirical force fields have dominated biomolecular simulation for over 50 years. Although widely used in drug discovery, crystal structure prediction, and biomolecular dynamics, they generally lack the accuracy and transferability required for first-principles predictive modeling. In this paper, we introduce MACE-OFF, a series of short range transferable force fields for organic molecules created using state-of-the-art machine learning technology and first-principles reference data computed with a high level of quantum mechanical theory. MACE-OFF demonstrates the remarkable capabilities of short range models by accurately predicting a wide variety of gas and condensed phase properties of molecular systems. It produces accurate, easy-to-converge dihedral torsion scans of unseen molecules, as well as reliable descriptions of molecular crystals and liquids, including quantum nuclear effects. We further demonstrate the capabilities of MACE-OFF by determining free energy surfaces in explicit solvent, as well as the folding dynamics of peptides.Finally, we simulate a fully solvated small protein, observing accurate secondary structure and vibrational spectrum. These developments enable first-principles simulations of molecular systems for the broader chemistry community at high accuracy and relatively low computational cost.

Methods for designing organic materials with desired properties have high potential impact across fields such as medicine, renewable energy, petrochemical engineering, and agriculture. However, using generative modeling to design substances with desired properties is difficult because candidate compounds must satisfy multiple constraints, including synthetic accessibility and other metrics that are intuitive to domain experts but challenging to quantify. We propose C5T5, a novel self-supervised pretraining method that enables transformers to make zero-shot select-and-replace edits, altering organic substances towards desired property values. C5T5 operates on IUPAC names -- a standardized molecular representation that intuitively encodes rich structural information for organic chemists but that has been largely ignored by the ML community. Our technique requires no edited molecule pairs to train and only a rough estimate of molecular properties, and it has the potential to model long-range dependencies and symmetric molecular structures more easily than graph-based methods. C5T5 also provides a powerful interface to domain experts: it grants users fine-grained control over the generative process by selecting and replacing IUPAC name fragments, which enables experts to leverage their intuitions about structure-activity relationships. We demonstrate C5T5's effectiveness on four physical properties relevant for drug discovery, showing that it learns successful and chemically intuitive strategies for altering molecules towards desired property values.

The size, diversity, and quality of pretraining datasets critically determine the generalization ability of foundation models. Despite their growing importance in chemoinformatics, the effectiveness of molecular representation learning has been hindered by limitations in existing small molecule datasets. To address this gap, we present MolPILE, large-scale, diverse, and rigorously curated collection of 222 million compounds, constructed from 6 large-scale databases using an automated curation pipeline. We present a comprehensive analysis of current pretraining datasets, highlighting considerable shortcomings for training ML models, and demonstrate how retraining existing models on MolPILE yields improvements in generalization performance. This work provides a standardized resource for model training, addressing the pressing need for an ImageNet-like dataset in molecular chemistry.

Polymers-macromolecular systems composed of repeating chemical units-constitute the molecular foundation of living organisms, while their synthetic counterparts drive transformative advances across medicine, consumer products, and energy technologies. While machine learning (ML) models have been trained on millions of quantum chemical atomistic simulations for materials and/or small molecular structures to enable efficient, accurate, and transferable predictions of chemical properties, polymers have largely not been included in prior datasets due to the computational expense of high quality electronic structure calculations on representative polymeric structures. Here, we address this shortcoming with the creation of the Open Polymers 2026 (OPoly26) dataset, which contains more than 6.57 million density functional theory (DFT) calculations on up to 360 atom clusters derived from polymeric systems, comprising over 1.2 billion total atoms. OPoly26 captures the chemical diversity that makes polymers intrinsically tunable and versatile materials, encompassing variations in monomer composition, degree of polymerization, chain architectures, and solvation environments. We show that augmenting ML model training with the OPoly26 dataset improves model performance for polymer prediction tasks. We also publicly release the OPoly26 dataset to help further the development of ML models for polymers, and more broadly, strive towards universal atomistic models.

Automated computational analysis of the vast chemical space is critical for numerous fields of research such as drug discovery and material science. Representation learning techniques have recently been employed with the primary objective of generating compact and informative numerical expressions of complex data. One approach to efficiently learn molecular representations is processing string-based notations of chemicals via natural language processing (NLP) algorithms. Majority of the methods proposed so far utilize SMILES notations for this purpose; however, SMILES is associated with numerous problems related to validity and robustness, which may prevent the model from effectively uncovering the knowledge hidden in the data. In this study, we propose SELFormer, a transformer architecture-based chemical language model that utilizes a 100% valid, compact and expressive notation, SELFIES, as input, in order to learn flexible and high-quality molecular representations. SELFormer is pre-trained on two million drug-like compounds and fine-tuned for diverse molecular property prediction tasks. Our performance evaluation has revealed that, SELFormer outperforms all competing methods, including graph learning-based approaches and SMILES-based chemical language models, on predicting aqueous solubility of molecules and adverse drug reactions. We also visualized molecular representations learned by SELFormer via dimensionality reduction, which indicated that even the pre-trained model can discriminate molecules with differing structural properties. We shared SELFormer as a programmatic tool, together with its datasets and pre-trained models. Overall, our research demonstrates the benefit of using the SELFIES notations in the context of chemical language modeling and opens up new possibilities for the design and discovery of novel drug candidates with desired features.

Models based on machine learning can enable accurate and fast molecular property predictions, which is of interest in drug discovery and material design. Various supervised machine learning models have demonstrated promising performance, but the vast chemical space and the limited availability of property labels make supervised learning challenging. Recently, unsupervised transformer-based language models pretrained on a large unlabelled corpus have produced state-of-the-art results in many downstream natural language processing tasks. Inspired by this development, we present molecular embeddings obtained by training an efficient transformer encoder model, MoLFormer, which uses rotary positional embeddings. This model employs a linear attention mechanism, coupled with highly distributed training, on SMILES sequences of 1.1 billion unlabelled molecules from the PubChem and ZINC datasets. We show that the learned molecular representation outperforms existing baselines, including supervised and self-supervised graph neural networks and language models, on several downstream tasks from ten benchmark datasets. They perform competitively on two others. Further analyses, specifically through the lens of attention, demonstrate that MoLFormer trained on chemical SMILES indeed learns the spatial relationships between atoms within a molecule. These results provide encouraging evidence that large-scale molecular language models can capture sufficient chemical and structural information to predict various distinct molecular properties, including quantum-chemical properties.

Chemical reaction prediction, involving forward synthesis and retrosynthesis prediction, is a fundamental problem in organic synthesis. A popular computational paradigm formulates synthesis prediction as a sequence-to-sequence translation problem, where the typical SMILES is adopted for molecule representations. However, the general-purpose SMILES neglects the characteristics of chemical reactions, where the molecular graph topology is largely unaltered from reactants to products, resulting in the suboptimal performance of SMILES if straightforwardly applied. In this article, we propose the root-aligned SMILES (R-SMILES), which specifies a tightly aligned one-to-one mapping between the product and the reactant SMILES for more efficient synthesis prediction. Due to the strict one-to-one mapping and reduced edit distance, the computational model is largely relieved from learning the complex syntax and dedicated to learning the chemical knowledge for reactions. We compare the proposed R-SMILES with various state-of-the-art baselines and show that it significantly outperforms them all, demonstrating the superiority of the proposed method.

We introduce FragAtlas-62M, a specialized foundation model trained on the largest fragment dataset to date. Built on the complete ZINC-22 fragment subset comprising over 62 million molecules, it achieves unprecedented coverage of fragment chemical space. Our GPT-2 based model (42.7M parameters) generates 99.90% chemically valid fragments. Validation across 12 descriptors and three fingerprint methods shows generated fragments closely match the training distribution (all effect sizes < 0.4). The model retains 53.6% of known ZINC fragments while producing 22% novel structures with practical relevance. We release FragAtlas-62M with training code, preprocessed data, documentation, and model weights to accelerate adoption.

Understanding the chemical structure from a graphical representation of a molecule is a challenging image caption task that would greatly benefit molecule-centric scientific discovery. Variations in molecular images and caption subtasks pose a significant challenge in both image representation learning and task modeling. Yet, existing methods only focus on a specific caption task that translates a molecular image into its graph structure, i.e., OCSR. In this paper, we propose the Optical Chemical Structure Understanding (OCSU) task, which extends OCSR to molecular image caption from motif level to molecule level and abstract level. We present two approaches for that, including an OCSR-based method and an end-to-end OCSR-free method. The proposed Double-Check achieves SOTA OCSR performance on real-world patent and journal article scenarios via attentive feature enhancement for local ambiguous atoms. Cascading with SMILES-based molecule understanding methods, it can leverage the power of existing task-specific models for OCSU. While Mol-VL is an end-to-end optimized VLM-based model. An OCSU dataset, Vis-CheBI20, is built based on the widely used CheBI20 dataset for training and evaluation. Extensive experimental results on Vis-CheBI20 demonstrate the effectiveness of the proposed approaches. Improving OCSR capability can lead to a better OCSU performance for OCSR-based approach, and the SOTA performance of Mol-VL demonstrates the great potential of end-to-end approach.

Large language models (LLMs) have gained widespread interest due to their ability to process human language and perform tasks on which they have not been explicitly trained. This is relevant for the chemical sciences, which face the problem of small and diverse datasets that are frequently in the form of text. LLMs have shown promise in addressing these issues and are increasingly being harnessed to predict chemical properties, optimize reactions, and even design and conduct experiments autonomously. However, we still have only a very limited systematic understanding of the chemical reasoning capabilities of LLMs, which would be required to improve models and mitigate potential harms. Here, we introduce "ChemBench," an automated framework designed to rigorously evaluate the chemical knowledge and reasoning abilities of state-of-the-art LLMs against the expertise of human chemists. We curated more than 7,000 question-answer pairs for a wide array of subfields of the chemical sciences, evaluated leading open and closed-source LLMs, and found that the best models outperformed the best human chemists in our study on average. The models, however, struggle with some chemical reasoning tasks that are easy for human experts and provide overconfident, misleading predictions, such as about chemicals' safety profiles. These findings underscore the dual reality that, although LLMs demonstrate remarkable proficiency in chemical tasks, further research is critical to enhancing their safety and utility in chemical sciences. Our findings also indicate a need for adaptations to chemistry curricula and highlight the importance of continuing to develop evaluation frameworks to improve safe and useful LLMs.

Self-supervised neural language models have recently achieved unprecedented success, from natural language processing to learning the languages of biological sequences and organic molecules. These models have demonstrated superior performance in the generation, structure classification, and functional predictions for proteins and molecules with learned representations. However, most of the masking-based pre-trained language models are not designed for generative design, and their black-box nature makes it difficult to interpret their design logic. Here we propose BLMM Crystal Transformer, a neural network based probabilistic generative model for generative and tinkering design of inorganic materials. Our model is built on the blank filling language model for text generation and has demonstrated unique advantages in learning the "materials grammars" together with high-quality generation, interpretability, and data efficiency. It can generate chemically valid materials compositions with as high as 89.7\% charge neutrality and 84.8\% balanced electronegativity, which are more than 4 and 8 times higher compared to a pseudo random sampling baseline. The probabilistic generation process of BLMM allows it to recommend tinkering operations based on learned materials chemistry and makes it useful for materials doping. Combined with the TCSP crysal structure prediction algorithm, We have applied our model to discover a set of new materials as validated using DFT calculations. Our work thus brings the unsupervised transformer language models based generative artificial intelligence to inorganic materials. A user-friendly web app has been developed for computational materials doping and can be accessed freely at www.materialsatlas.org/blmtinker.

Generating molecules that satisfy precise numeric constraints over multiple physicochemical properties is critical and challenging. Although large language models (LLMs) are expressive, they struggle with precise multi-objective control and numeric reasoning without external structure and feedback. We introduce M olGen, a fragment-level, retrieval-augmented, two-stage framework for molecule generation under multi-property constraints. Stage I : Prototype generation: a multi-agent reasoner performs retrieval-anchored, fragment-level edits to produce a candidate near the feasible region. Stage II : RL-based fine-grained optimization: a fragment-level optimizer trained with Group Relative Policy Optimization (GRPO) applies one- or multi-hop refinements to explicitly minimize the property errors toward our target while regulating edit complexity and deviation from the prototype. A large, automatically curated dataset with reasoning chains of fragment edits and measured property deltas underpins both stages, enabling deterministic, reproducible supervision and controllable multi-hop reasoning. Unlike prior work, our framework better reasons about molecules by leveraging fragments and supports controllable refinement toward numeric targets. Experiments on generation under two sets of property constraints (QED, LogP, Molecular Weight and HOMO, LUMO) show consistent gains in validity and precise satisfaction of multi-property targets, outperforming strong LLMs and graph-based algorithms.

Large language models (LLMs) have recently demonstrated promising capabilities in chemistry tasks while still facing challenges due to outdated pretraining knowledge and the difficulty of incorporating specialized chemical expertise. To address these issues, we propose an LLM-based agent that synergistically integrates 137 external chemical tools created ranging from basic information retrieval to complex reaction predictions, and a dataset curation pipeline to generate the dataset ChemToolBench that facilitates both effective tool selection and precise parameter filling during fine-tuning and evaluation. We introduce a Hierarchical Evolutionary Monte Carlo Tree Search (HE-MCTS) framework, enabling independent optimization of tool planning and execution. By leveraging self-generated data, our approach supports step-level fine-tuning (FT) of the policy model and training task-adaptive PRM and ORM that surpass GPT-4o. Experimental evaluations demonstrate that our approach significantly improves performance in Chemistry QA and discovery tasks, offering a robust solution to integrate specialized tools with LLMs for advanced chemical applications. All datasets and code are available at https://github.com/AI4Chem/ChemistryAgent .

Large pretrained models such as GPT-3 have had tremendous impact on modern natural language processing by leveraging self-supervised learning to learn salient representations that can be used to readily finetune on a wide variety of downstream tasks. We investigate the possibility of transferring such advances to molecular machine learning by building a chemical foundation model, ChemBERTa-2, using the language of SMILES. While labeled data for molecular prediction tasks is typically scarce, libraries of SMILES strings are readily available. In this work, we build upon ChemBERTa by optimizing the pretraining process. We compare multi-task and self-supervised pretraining by varying hyperparameters and pretraining dataset size, up to 77M compounds from PubChem. To our knowledge, the 77M set constitutes one of the largest datasets used for molecular pretraining to date. We find that with these pretraining improvements, we are competitive with existing state-of-the-art architectures on the MoleculeNet benchmark suite. We analyze the degree to which improvements in pretraining translate to improvement on downstream tasks.

Molecular Representation Learning (MRL) has proven impactful in numerous biochemical applications such as drug discovery and enzyme design. While Graph Neural Networks (GNNs) are effective at learning molecular representations from a 2D molecular graph or a single 3D structure, existing works often overlook the flexible nature of molecules, which continuously interconvert across conformations via chemical bond rotations and minor vibrational perturbations. To better account for molecular flexibility, some recent works formulate MRL as an ensemble learning problem, focusing on explicitly learning from a set of conformer structures. However, most of these studies have limited datasets, tasks, and models. In this work, we introduce the first MoleculAR Conformer Ensemble Learning (MARCEL) benchmark to thoroughly evaluate the potential of learning on conformer ensembles and suggest promising research directions. MARCEL includes four datasets covering diverse molecule- and reaction-level properties of chemically diverse molecules including organocatalysts and transition-metal catalysts, extending beyond the scope of common GNN benchmarks that are confined to drug-like molecules. In addition, we conduct a comprehensive empirical study, which benchmarks representative 1D, 2D, and 3D molecular representation learning models, along with two strategies that explicitly incorporate conformer ensembles into 3D MRL models. Our findings reveal that direct learning from an accessible conformer space can improve performance on a variety of tasks and models.

Machine Learning Force Fields (MLFFs) are a promising alternative to expensive ab initio quantum mechanical molecular simulations. Given the diversity of chemical spaces that are of interest and the cost of generating new data, it is important to understand how MLFFs generalize beyond their training distributions. In order to characterize and better understand distribution shifts in MLFFs, we conduct diagnostic experiments on chemical datasets, revealing common shifts that pose significant challenges, even for large foundation models trained on extensive data. Based on these observations, we hypothesize that current supervised training methods inadequately regularize MLFFs, resulting in overfitting and learning poor representations of out-of-distribution systems. We then propose two new methods as initial steps for mitigating distribution shifts for MLFFs. Our methods focus on test-time refinement strategies that incur minimal computational cost and do not use expensive ab initio reference labels. The first strategy, based on spectral graph theory, modifies the edges of test graphs to align with graph structures seen during training. Our second strategy improves representations for out-of-distribution systems at test-time by taking gradient steps using an auxiliary objective, such as a cheap physical prior. Our test-time refinement strategies significantly reduce errors on out-of-distribution systems, suggesting that MLFFs are capable of and can move towards modeling diverse chemical spaces, but are not being effectively trained to do so. Our experiments establish clear benchmarks for evaluating the generalization capabilities of the next generation of MLFFs. Our code is available at https://tkreiman.github.io/projects/mlff_distribution_shifts/.

We seek to automate the design of molecules based on specific chemical properties. In computational terms, this task involves continuous embedding and generation of molecular graphs. Our primary contribution is the direct realization of molecular graphs, a task previously approached by generating linear SMILES strings instead of graphs. Our junction tree variational autoencoder generates molecular graphs in two phases, by first generating a tree-structured scaffold over chemical substructures, and then combining them into a molecule with a graph message passing network. This approach allows us to incrementally expand molecules while maintaining chemical validity at every step. We evaluate our model on multiple tasks ranging from molecular generation to optimization. Across these tasks, our model outperforms previous state-of-the-art baselines by a significant margin.

Molecular representation is a foundational element in our understanding of the physical world. Its importance ranges from the fundamentals of chemical reactions to the design of new therapies and materials. Previous molecular machine learning models have employed strings, fingerprints, global features, and simple molecular graphs that are inherently information-sparse representations. However, as the complexity of prediction tasks increases, the molecular representation needs to encode higher fidelity information. This work introduces a novel approach to infusing quantum-chemical-rich information into molecular graphs via stereoelectronic effects. We show that the explicit addition of stereoelectronic interactions significantly improves the performance of molecular machine learning models. Furthermore, stereoelectronics-infused representations can be learned and deployed with a tailored double graph neural network workflow, enabling its application to any downstream molecular machine learning task. Finally, we show that the learned representations allow for facile stereoelectronic evaluation of previously intractable systems, such as entire proteins, opening new avenues of molecular design.

Large language models (LLMs) have made impressive progress in chemistry applications, including molecular property prediction, molecular generation, experimental protocol design, etc. However, the community lacks a dialogue-based model specifically designed for chemistry. The challenge arises from the fact that most chemical data and scientific knowledge are primarily stored in structured databases, and the direct use of these structured data compromises the model's ability to maintain coherent dialogue. To tackle this issue, we develop a novel template-based instruction construction method that transforms structured knowledge into plain dialogue, making it suitable for language model training. By leveraging this approach, we develop ChemLLM, the first large language model dedicated to chemistry, capable of performing various tasks across chemical disciplines with smooth dialogue interaction. ChemLLM beats GPT-3.5 on all three principal tasks in chemistry, i.e., name conversion, molecular caption, and reaction prediction, and surpasses GPT-4 on two of them. Remarkably, ChemLLM also shows exceptional adaptability to related mathematical and physical tasks despite being trained mainly on chemical-centric corpora. Furthermore, ChemLLM demonstrates proficiency in specialized NLP tasks within chemistry, such as literature translation and cheminformatic programming. ChemLLM opens up a new avenue for exploration within chemical studies, while our method of integrating structured chemical knowledge into dialogue systems sets a new frontier for developing LLMs across various scientific fields. Codes, Datasets, and Model weights are publicly accessible at hf.co/AI4Chem/ChemLLM-7B-Chat.

Molecular structure elucidation involves deducing a molecule's structure from various types of spectral data, which is crucial in chemical experimental analysis. While large language models (LLMs) have shown remarkable proficiency in analyzing and reasoning through complex tasks, they still encounter substantial challenges in molecular structure elucidation. We identify that these challenges largely stem from LLMs' limited grasp of specialized chemical knowledge. In this work, we introduce a Knowledge-enhanced reasoning framework for Molecular Structure Elucidation (K-MSE), leveraging Monte Carlo Tree Search for test-time scaling as a plugin. Specifically, we construct an external molecular substructure knowledge base to extend the LLMs' coverage of the chemical structure space. Furthermore, we design a specialized molecule-spectrum scorer to act as a reward model for the reasoning process, addressing the issue of inaccurate solution evaluation in LLMs. Experimental results show that our approach significantly boosts performance, particularly gaining more than 20% improvement on both GPT-4o-mini and GPT-4o. Our code is available at https://github.com/HICAI-ZJU/K-MSE.

Crystal structure determination from powder diffraction patterns is a complex challenge in materials science, often requiring extensive expertise and computational resources. This study introduces DiffractGPT, a generative pre-trained transformer model designed to predict atomic structures directly from X-ray diffraction (XRD) patterns. By capturing the intricate relationships between diffraction patterns and crystal structures, DiffractGPT enables fast and accurate inverse design. Trained on thousands of atomic structures and their simulated XRD patterns from the JARVIS-DFT dataset, we evaluate the model across three scenarios: (1) without chemical information, (2) with a list of elements, and (3) with an explicit chemical formula. The results demonstrate that incorporating chemical information significantly enhances prediction accuracy. Additionally, the training process is straightforward and fast, bridging gaps between computational, data science, and experimental communities. This work represents a significant advancement in automating crystal structure determination, offering a robust tool for data-driven materials discovery and design.

The automated analysis of chemical literature holds promise to accelerate discovery in fields such as material science and drug development. In particular, search capabilities for chemical structures and Markush structures (chemical structure templates) within patent documents are valuable, e.g., for prior-art search. Advancements have been made in the automatic extraction of chemical structures from text and images, yet the Markush structures remain largely unexplored due to their complex multi-modal nature. In this work, we present MarkushGrapher, a multi-modal approach for recognizing Markush structures in documents. Our method jointly encodes text, image, and layout information through a Vision-Text-Layout encoder and an Optical Chemical Structure Recognition vision encoder. These representations are merged and used to auto-regressively generate a sequential graph representation of the Markush structure along with a table defining its variable groups. To overcome the lack of real-world training data, we propose a synthetic data generation pipeline that produces a wide range of realistic Markush structures. Additionally, we present M2S, the first annotated benchmark of real-world Markush structures, to advance research on this challenging task. Extensive experiments demonstrate that our approach outperforms state-of-the-art chemistry-specific and general-purpose vision-language models in most evaluation settings. Code, models, and datasets will be available.

The task of chemical reaction predictions (CRPs) plays a pivotal role in advancing drug discovery and material science. However, its effectiveness is constrained by the vast and uncertain chemical reaction space and challenges in capturing reaction selectivity, particularly due to existing methods' limitations in exploiting the data's inherent knowledge. To address these challenges, we introduce a data-curated self-feedback knowledge elicitation approach. This method starts from iterative optimization of molecular representations and facilitates the extraction of knowledge on chemical reaction types (RTs). Then, we employ adaptive prompt learning to infuse the prior knowledge into the large language model (LLM). As a result, we achieve significant enhancements: a 14.2% increase in retrosynthesis prediction accuracy, a 74.2% rise in reagent prediction accuracy, and an expansion in the model's capability for handling multi-task chemical reactions. This research offers a novel paradigm for knowledge elicitation in scientific research and showcases the untapped potential of LLMs in CRPs.

Large-scale datasets have enabled highly accurate machine learning interatomic potentials (MLIPs) for general-purpose heterogeneous catalysis modeling. There are, however, some limitations in what can be treated with these potentials because of gaps in the underlying training data. To extend these capabilities, we introduce AQCat25, a complementary dataset of 13.5 million density functional theory (DFT) single point calculations designed to improve the treatment of systems where spin polarization and/or higher fidelity are critical. We also investigate methodologies for integrating new datasets, such as AQCat25, with the broader Open Catalyst 2020 (OC20) dataset to create spin-aware models without sacrificing generalizability. We find that directly tuning a general model on AQCat25 leads to catastrophic forgetting of the original dataset's knowledge. Conversely, joint training strategies prove effective for improving accuracy on the new data without sacrificing general performance. This joint approach introduces a challenge, as the model must learn from a dataset containing both mixed-fidelity calculations and mixed-physics (spin-polarized vs. unpolarized). We show that explicitly conditioning the model on this system-specific metadata, for example by using Feature-wise Linear Modulation (FiLM), successfully addresses this challenge and further enhances model accuracy. Ultimately, our work establishes an effective protocol for bridging DFT fidelity domains to advance the predictive power of foundational models in catalysis.

Progress in computer-aided synthesis planning (CASP) is obscured by the lack of standardized evaluation infrastructure and the reliance on metrics that prioritize topological completion over chemical validity. We introduce RetroCast, a unified evaluation suite that standardizes heterogeneous model outputs into a common schema to enable statistically rigorous, apples-to-apples comparison. The framework includes a reproducible benchmarking pipeline with stratified sampling and bootstrapped confidence intervals, accompanied by SynthArena, an interactive platform for qualitative route inspection. We utilize this infrastructure to evaluate leading search-based and sequence-based algorithms on a new suite of standardized benchmarks. Our analysis reveals a divergence between "solvability" (stock-termination rate) and route quality; high solvability scores often mask chemical invalidity or fail to correlate with the reproduction of experimental ground truths. Furthermore, we identify a "complexity cliff" in which search-based methods, despite high solvability rates, exhibit a sharp performance decay in reconstructing long-range synthetic plans compared to sequence-based approaches. We release the full framework, benchmark definitions, and a standardized database of model predictions to support transparent and reproducible development in the field.

Machine-learned force fields have transformed the atomistic modelling of materials by enabling simulations of ab initio quality on unprecedented time and length scales. However, they are currently limited by: (i) the significant computational and human effort that must go into development and validation of potentials for each particular system of interest; and (ii) a general lack of transferability from one chemical system to the next. Here, using the state-of-the-art MACE architecture we introduce a single general-purpose ML model, trained on a public database of 150k inorganic crystals, that is capable of running stable molecular dynamics on molecules and materials. We demonstrate the power of the MACE-MP-0 model -- and its qualitative and at times quantitative accuracy -- on a diverse set problems in the physical sciences, including the properties of solids, liquids, gases, and chemical reactions. The model can be applied out of the box and as a starting or "foundation model" for any atomistic system of interest and is thus a step towards democratising the revolution of ML force fields by lowering the barriers to entry.

Identifying a small molecule from its mass spectrum is the primary open problem in computational metabolomics. This is typically cast as information retrieval: an unknown spectrum is matched against spectra predicted computationally from a large database of chemical structures. However, current approaches to spectrum prediction model the output space in ways that force a tradeoff between capturing high resolution mass information and tractable learning. We resolve this tradeoff by casting spectrum prediction as a mapping from an input molecular graph to a probability distribution over molecular formulas. We discover that a large corpus of mass spectra can be closely approximated using a fixed vocabulary constituting only 2% of all observed formulas. This enables efficient spectrum prediction using an architecture similar to graph classification - GrAFF-MS - achieving significantly lower prediction error and orders-of-magnitude faster runtime than state-of-the-art methods.

Knowledge of mixtures' phase equilibria is crucial in nature and technical chemistry. Phase equilibria calculations of mixtures require activity coefficients. However, experimental data on activity coefficients is often limited due to high cost of experiments. For an accurate and efficient prediction of activity coefficients, machine learning approaches have been recently developed. However, current machine learning approaches still extrapolate poorly for activity coefficients of unknown molecules. In this work, we introduce the SMILES-to-Properties-Transformer (SPT), a natural language processing network to predict binary limiting activity coefficients from SMILES codes. To overcome the limitations of available experimental data, we initially train our network on a large dataset of synthetic data sampled from COSMO-RS (10 Million data points) and then fine-tune the model on experimental data (20 870 data points). This training strategy enables SPT to accurately predict limiting activity coefficients even for unknown molecules, cutting the mean prediction error in half compared to state-of-the-art models for activity coefficient predictions such as COSMO-RS, UNIFAC, and improving on recent machine learning approaches.

The recent success of large foundation models in artificial intelligence has prompted the emergence of chemical pre-trained models. Despite the growing interest in large molecular pre-trained models that provide informative representations for downstream tasks, attempts for multimodal pre-training approaches on the molecule domain were limited. To address this, we present a novel multimodal molecular pre-trained model that incorporates the modalities of structure and biochemical properties, drawing inspiration from recent advances in multimodal learning techniques. Our proposed model pipeline of data handling and training objectives aligns the structure/property features in a common embedding space, which enables the model to regard bidirectional information between the molecules' structure and properties. These contributions emerge synergistic knowledge, allowing us to tackle both multimodal and unimodal downstream tasks through a single model. Through extensive experiments, we demonstrate that our model shows remarkable capabilities in solving various meaningful chemical challenges, including conditional molecule generation, property prediction, molecule classification, and reaction prediction.

Accurate prediction of protein-ligand binding affinities is crucial in drug discovery, particularly during hit-to-lead and lead optimization phases, however, limitations in ligand force fields continue to impact prediction accuracy. In this work, we validate relative binding free energy (RBFE) accuracy using neural network potentials (NNPs) for the ligands. We utilize a novel NNP model, AceForce 1.0, based on the TensorNet architecture for small molecules that broadens the applicability to diverse drug-like compounds, including all important chemical elements and supporting charged molecules. Using established benchmarks, we show overall improved accuracy and correlation in binding affinity predictions compared with GAFF2 for molecular mechanics and ANI2-x for NNPs. Slightly less accuracy but comparable correlations with OPLS4. We also show that we can run the NNP simulations at 2 fs timestep, at least two times larger than previous NNP models, providing significant speed gains. The results show promise for further evolutions of free energy calculations using NNPs while demonstrating its practical use already with the current generation. The code and NNP model are publicly available for research use.

Chemical language models (CLMs) are prominent for their effectiveness in exploring chemical space and enabling molecular engineering. However, while exploring chemical-linguistic space, CLMs suffer from the gap between natural language and molecular representations. This challenge is primarily due to the inherent modeling differences between molecules and texts: molecules operate unified modeling to learn chemical space, while natural language sequentially models the semantic space. Additionally, the limited availability of high-quality text-to-molecule datasets further exacerbates this challenge. To address the problem, we first verified the information bias in molecular representations from different perspectives. We then developed the Heterogeneous Molecular Encoding (HME) framework, a unified molecular encoder compressing the molecular features from fragment sequence, topology, and conformation with Q-learning. To better model chemical-linguistic space, we further constructed the MCMoD dataset, which contains over one million molecules with various conditions, including properties, fragments, and descriptions. Experimentally, HME promotes CLMs to achieve chemical-linguistic sharing space exploration: (1) chemical space exploration with linguistic guidance, where HME achieves significant improvements (+37.8\% FCD) for molecular design in multiple constraints, even in zero-shot scenarios; (2) linguistic space exploration with molecular guidance, where HME generates textual descriptions with high qualities (+11.6\% BLEU) for molecules. These results highlight the precision of HME in handling multi-objective and cross-domain tasks, as well as its remarkable generalization capability on unseen task combinations. HME offers a new perspective on navigating chemical-linguistic sharing space, advancing the potential of CLMs in both fundamental research and practical applications in chemistry.

Although large language models (LLMs) have significant potential to advance chemical discovery, current LLMs lack core chemical knowledge, produce unreliable reasoning trajectories, and exhibit suboptimal performance across diverse chemical tasks. To address these challenges, we propose Chem-R, a generalizable Chemical Reasoning model designed to emulate the deliberative processes of chemists. Chem-R is trained through a three-phase framework that progressively builds advanced reasoning capabilities, including: 1) Chemical Foundation Training, which establishes core chemical knowledge. 2) Chemical Reasoning Protocol Distillation, incorporating structured, expert-like reasoning traces to guide systematic and reliable problem solving. 3) Multi-task Group Relative Policy Optimization that optimizes the model for balanced performance across diverse molecular- and reaction-level tasks. This structured pipeline enables Chem-R to achieve state-of-the-art performance on comprehensive benchmarks, surpassing leading large language models, including Gemini-2.5-Pro and DeepSeek-R1, by up to 46% on molecular tasks and 66% on reaction tasks. Meanwhile, Chem-R also consistently outperforms the existing chemical foundation models across both molecular and reaction level tasks. These results highlight Chem-R's robust generalization, interpretability, and potential as a foundation for next-generation AI-driven chemical discovery.

We introduce Suiren-1.0, a family of molecular foundation models for the accurate modeling of diverse organic systems. Suiren-1.0 comprising three specialized variants (Suiren-Base, Suiren-Dimer, and Suiren-ConfAvg) is integrated within an algorithmic framework that bridges the gap between 3D conformational geometry and 2D statistical ensemble spaces. We first pre-train Suiren-Base (1.8B parameters) on a 70M-sample Density Functional Theory dataset using spatial self-supervision and SE(3)-equivariant architectures, achieving robust performance in quantum property prediction. Suiren-Dimer extends this capability through continued pre-training on 13.5M intermolecular interaction samples. To enable efficient downstream application, we propose Conformation Compression Distillation (CCD), a diffusion-based framework that distills complex 3D structural representations into 2D conformation-averaged representations. This yields the lightweight Suiren-ConfAvg, which generates high-fidelity representations from SMILES or molecular graphs. Our extensive evaluations demonstrate that Suiren-1.0 establishes state-of-the-art results across a range of tasks. All models and benchmarks are open-sourced.

For the large and chemically diverse GMTKN55 benchmark suite, we have studied the performance of density-corrected density functional theory (HF-DFT), compared to self-consistent DFT, for several pure and hybrid GGA and meta-GGA exchange-correlation (XC) functionals (PBE, BLYP, TPSS, SCAN) as a function of the percentage of HF exchange in the hybrid. The D4 empirical dispersion correction has been added throughout. For subsets dominated by dynamical correlation -- particularly noncovalent interaction subsets -- HF-DFT is highly beneficial, particularly at low HF exchange percentages. For subsets with significant static correlation (i.e., where a Hartree-Fock determinant is not a good zero-order wavefunction), HF-DFT may do more harm than good. While the self-consistent series show optima at or near 37.5% (i.e., 3/8) for all four XC functionals -- consistent with Grimme's proposal of the PBE38 functional -- HF-BnLYP-D4, HF-PBEn-D4, and HF-TPSSn-D4 all exhibit minima nearer 25% (i.e., 1/4). Intriguingly, for HF-SCANn-D4, the minimum is near 10%, but the weighted mean absolute error (WTMAD2) for GMTKN55 is only barely lower than that of HF-SCAN-D4 (i.e., where the post-HF step is a pure meta-GGA). The latter becomes an attractive option, only slightly more costly than pure Hartree-Fock, and devoid of adjustable parameters other than the three in the dispersion correction. Moreover, its WTMAD2 is only surpassed by the highly empirical M06-2X and by the combinatorically optimized empirical range-separated hybrids wB97X-V and wB97M-V.

Effectively leveraging data from multiple quantum-chemical methods is essential for building machine-learned force fields (MLFFs) that are applicable to a wide range of chemical systems. This study systematically investigates two multi-fidelity training strategies, pre-training/fine-tuning and multi-headed training, to elucidate the mechanisms underpinning their success. We identify key factors driving the efficacy of pre-training followed by fine-tuning, but find that internal representations learned during pre-training are inherently method-specific, requiring adaptation of the model backbone during fine-tuning. Multi-headed models offer an extensible alternative, enabling simultaneous training on multiple fidelities. We demonstrate that a multi-headed model learns method-agnostic representations that allow for accurate predictions across multiple label sources. While this approach introduces a slight accuracy compromise compared to sequential fine-tuning, it unlocks new cost-efficient data generation strategies and paves the way towards developing universal MLFFs.

We propose fine-tuning large language models for generation of stable materials. While unorthodox, fine-tuning large language models on text-encoded atomistic data is simple to implement yet reliable, with around 90% of sampled structures obeying physical constraints on atom positions and charges. Using energy above hull calculations from both learned ML potentials and gold-standard DFT calculations, we show that our strongest model (fine-tuned LLaMA-2 70B) can generate materials predicted to be metastable at about twice the rate (49% vs 28%) of CDVAE, a competing diffusion model. Because of text prompting's inherent flexibility, our models can simultaneously be used for unconditional generation of stable material, infilling of partial structures and text-conditional generation. Finally, we show that language models' ability to capture key symmetries of crystal structures improves with model scale, suggesting that the biases of pretrained LLMs are surprisingly well-suited for atomistic data.

Compound identification and structure annotation from mass spectra is a well-established task widely applied in drug detection, criminal forensics, small molecule biomarker discovery and chemical engineering. We propose SpecTUS: Spectral Translator for Unknown Structures, a deep neural model that addresses the task of structural annotation of small molecules from low-resolution gas chromatography electron ionization mass spectra (GC-EI-MS). Our model analyzes the spectra in de novo manner -- a direct translation from the spectra into 2D-structural representation. Our approach is particularly useful for analyzing compounds unavailable in spectral libraries. In a rigorous evaluation of our model on the novel structure annotation task across different libraries, we outperformed standard database search techniques by a wide margin. On a held-out testing set, including 28267 spectra from the NIST database, we show that our model's single suggestion perfectly reconstructs 43\% of the subset's compounds. This single suggestion is strictly better than the candidate of the database hybrid search (common method among practitioners) in 76\% of cases. In a~still affordable scenario of~10 suggestions, perfect reconstruction is achieved in 65\%, and 84\% are better than the hybrid search.

Central to our understanding of chemical reactivity is the principle of mass conservation, which is fundamental for ensuring physical consistency, balancing equations, and guiding reaction design. However, data-driven computational models for tasks such as reaction product prediction rarely abide by this most basic constraint. In this work, we recast the problem of reaction prediction as a problem of electron redistribution using the modern deep generative framework of flow matching. Our model, FlowER, overcomes limitations inherent in previous approaches by enforcing exact mass conservation, thereby resolving hallucinatory failure modes, recovering mechanistic reaction sequences for unseen substrate scaffolds, and generalizing effectively to out-of-domain reaction classes with extremely data-efficient fine-tuning. FlowER additionally enables estimation of thermodynamic or kinetic feasibility and manifests a degree of chemical intuition in reaction prediction tasks. This inherently interpretable framework represents a significant step in bridging the gap between predictive accuracy and mechanistic understanding in data-driven reaction outcome prediction.

Question Answering (QA) effectively evaluates language models' reasoning and knowledge depth. While QA datasets are plentiful in areas like general domain and biomedicine, academic chemistry is less explored. Chemical QA plays a crucial role in both education and research by effectively translating complex chemical information into readily understandable format. Addressing this gap, we introduce ScholarChemQA, a large-scale QA dataset constructed from chemical papers. This dataset reflects typical real-world challenges, including an imbalanced data distribution and a substantial amount of unlabeled data that can be potentially useful. Correspondingly, we introduce a QAMatch model, specifically designed to effectively answer chemical questions by fully leveraging our collected data. We first address the issue of imbalanced label distribution by re-weighting the instance-wise loss based on the inverse frequency of each class, ensuring minority classes are not dominated by majority ones during optimization. Next, we utilize the unlabeled data to enrich the learning process, generating a variety of augmentations based on a SoftMix operation and ensuring their predictions align with the same target, i.e., pseudo-labels. To ensure the quality of the pseudo-labels, we propose a calibration procedure aimed at closely aligning the pseudo-label estimates of individual samples with a desired ground truth distribution. Experiments show that our QAMatch significantly outperforms the recent similar-scale baselines and Large Language Models (LLMs) not only on our ScholarChemQA dataset but also on four benchmark datasets. We hope our benchmark and model can facilitate and promote more research on chemical QA.

Multimodal large language models (MLLMs) have made impressive progress in many applications in recent years. However, chemical MLLMs that can handle cross-modal understanding and generation remain underexplored. To fill this gap, in this paper, we propose ChemMLLM, a unified chemical multimodal large language model for molecule understanding and generation. Also, we design five multimodal tasks across text, molecular SMILES strings, and image, and curate the datasets. We benchmark ChemMLLM against a range of general leading MLLMs and Chemical LLMs on these tasks. Experimental results show that ChemMLLM achieves superior performance across all evaluated tasks. For example, in molecule image optimization task, ChemMLLM outperforms the best baseline (GPT-4o) by 118.9\% (4.27 vs 1.95 property improvement). The code is publicly available at https://github.com/bbsbz/ChemMLLM.git.

Large Language Models (LLMs) with strong abilities in natural language processing tasks have emerged and have been rapidly applied in various kinds of areas such as science, finance and software engineering. However, the capability of LLMs to advance the field of chemistry remains unclear. In this paper,we establish a comprehensive benchmark containing 8 practical chemistry tasks, including 1) name prediction, 2) property prediction, 3) yield prediction, 4) reaction prediction, 5) retrosynthesis (prediction of reactants from products), 6)text-based molecule design, 7) molecule captioning, and 8) reagent selection. Our analysis draws on widely recognized datasets including BBBP, Tox21, PubChem, USPTO, and ChEBI, facilitating a broad exploration of the capacities of LLMs within the context of practical chemistry. Three GPT models (GPT-4, GPT-3.5,and Davinci-003) are evaluated for each chemistry task in zero-shot and few-shot in-context learning settings with carefully selected demonstration examples and specially crafted prompts. The key results of our investigation are 1) GPT-4 outperforms the other two models among the three evaluated; 2) GPT models exhibit less competitive performance in tasks demanding precise understanding of molecular SMILES representation, such as reaction prediction and retrosynthesis;3) GPT models demonstrate strong capabilities in text-related explanation tasks such as molecule captioning; and 4) GPT models exhibit comparable or better performance to classical machine learning models when applied to chemical problems that can be transformed into classification or ranking tasks, such as property prediction, and yield prediction.

The tradeoff between precision and performance in molecular simulations can nowadays be addressed by machine-learned force fields (MLFF), which combine ab initio accuracy with force field numerical efficiency. Different from conventional force fields however, incorporating relevant electronic degrees of freedom into MLFFs becomes important. Here, we implement an equivariant transformer that embeds molecular net charge and spin state without additional neural network parameters. The model trained on a singlet/triplet non-correlated CH2 dataset can identify different spin states and shows state-of-the-art extrapolation capability. Therein, self-attention sensibly captures non-local effects, which, as we show, can be finely tuned over the network hyper-parameters. We indeed found that Softmax activation functions utilised in the self-attention mechanism of graph networks outperformed ReLU-like functions in prediction accuracy. Increasing the attention temperature from τ= d to 2d further improved the extrapolation capability, indicating a weighty role of nonlocality. Additionally, a weight initialisation method was purposed that sensibly accelerated the training process.