arXiv subjects

Adrian Roitberg

Publications and source records attributed to Adrian Roitberg.

10 recordsLinked to original sources

arXiv2026

MolCrystalFlow: Molecular Crystal Structure Prediction via Flow Matching

Molecular crystal structure prediction represents a grand challenge in computational chemistry due to large sizes of constituent molecules and complex intra- and intermolecular interactions. While generative modeling has revolutionized structure discovery for molecules, inorganic solids, and metal-organic frameworks, extending such approaches to fully periodic molecular crystals is still elusive. Here, we present MolCrystalFlow, a flow-based generative model for molecular crystal structure prediction. The framework disentangles intramolecular complexity from intermolecular packing by embedding molecules as rigid bodies and jointly learning the lattice matrix, molecular orientations, and centroid positions. Centroids and orientations are represented on their native Riemannian manifolds, allowing geodesic flow construction and graph neural network operations that respects geometric symmetries. We benchmark our model against a state-of-the-art generative model (MOFFlow) for large-size periodic crystals and a rule-based structure generation method (Genarris) on two open-source molecular crystal datasets. MolCrystalFlow outperforms MOFFlow while achieving competitive performance against Genarris. We also demonstrate an integration of MolCrystalFlow model with universal machine learning potential to accelerate molecular crystal structure prediction, paving the way for data-driven generative discovery of molecular crystals.

cs.LG↗

arXiv2025

MolGuidance: Advanced Guidance Strategies for Conditional Molecular Generation with Flow Matching

Key objectives in conditional molecular generation include ensuring chemical validity, aligning generated molecules with target properties, promoting structural diversity, and enabling efficient sampling for discovery. Recent advances in computer vision introduced a range of new guidance strategies for generative models, many of which can be adapted to support these goals. In this work, we integrate state-of-the-art guidance methods -- including classifier-free guidance, autoguidance, and model guidance -- in a leading molecule generation framework built on an SE(3)-equivariant flow matching process. We propose a hybrid guidance strategy that separately guides continuous and discrete molecular modalities -- operating on velocity fields and predicted logits, respectively -- while jointly optimizing their guidance scales via Bayesian optimization. Our implementation, benchmarked on the QM9 and QMe14S datasets, achieves new state-of-the-art performance in property alignment for de novo molecular generation. The generated molecules also exhibit high structural validity. Furthermore, we systematically compare the strengths and limitations of various guidance methods, offering insights into their broader applicability.

cs.LG↗

arXiv2025

Guided Diffusion for the Discovery of New Superconductors

The inverse design of materials with specific desired properties, such as high-temperature superconductivity, represents a formidable challenge in materials science due to the vastness of chemical and structural space. We present a guided diffusion framework to accelerate the discovery of novel superconductors. A DiffCSP foundation model is pretrained on the Alexandria Database and fine-tuned on 7,183 superconductors with first principles derived labels. Employing classifier-free guidance, we sample 200,000 structures, which lead to 34,027 unique candidates. A multistage screening process that combines machine learning and density functional theory (DFT) calculations to assess stability and electronic properties, identifies 773 candidates with DFT-calculated $T_\mathrm{c}>5$ K. Notably, our generative model demonstrates effective property-driven design. Our computational findings were validated against experimental synthesis and characterization performed as part of this work, which highlighted challenges in sparsely charted chemistries. This end-to-end workflow accelerates superconductor discovery while underscoring the challenge of predicting and synthesizing experimentally realizable materials.

cond-mat.supr-con↗

arXiv2025

All that structure matches does not glitter

Generative models for materials, especially inorganic crystals, hold potential to transform the theoretical prediction of novel compounds and structures. Advancement in this field depends 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 task$\unicode{x2014}$generating 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 $\approx$40% 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 and MP-20 datasets. 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 $N$, one with enantiomorphs, and two containing only identical structures but with different unit cells. We also propose new splits for datasets with polymorphs, ensuring that 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.

cs.LG↗

arXiv2025

PropMolFlow: Property-Guided Molecule Generation with Geometry-Complete Flow Matching

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, an 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 achieves competitive performance against previous SOTA diffusion models in conditional molecule generation while maintaining high structural stability and validity. Additionally, it enables faster sampling speed with fewer time steps compared to baseline models. We highlight the importance of validating the properties of generated molecules through DFT calculations. Furthermore, we introduce a task to assess the model's ability to propose molecules with underrepresented property values, assessing its capacity for out-of-distribution generalization.

physics.chem-ph↗

arXiv2025

Open Materials Generation with Stochastic Interpolants

The discovery of new materials is essential for enabling technological advancements. Computational approaches for predicting novel materials must effectively learn the manifold of stable crystal structures within an infinite design space. We introduce Open Materials Generation (OMatG), a unifying framework for the generative design and discovery of inorganic crystalline materials. OMatG employs stochastic interpolants (SI) to bridge an arbitrary base distribution to the target distribution of inorganic crystals via a broad class of tunable stochastic processes, encompassing both diffusion models and flow matching as special cases. In this work, we adapt the SI framework by integrating an equivariant graph representation of crystal structures and extending it to account for periodic boundary conditions in unit cell representations. Additionally, we couple the SI flow over spatial coordinates and lattice vectors with discrete flow matching for atomic species. We benchmark OMatG's performance on two tasks: Crystal Structure Prediction (CSP) for specified compositions, and 'de novo' generation (DNG) aimed at discovering stable, novel, and unique structures. In our ground-up implementation of OMatG, we refine and extend both CSP and DNG metrics compared to previous works. OMatG establishes a new state of the art in generative modeling for materials discovery, outperforming purely flow-based and diffusion-based implementations. These results underscore the importance of designing flexible deep learning frameworks to accelerate progress in materials science. The OMatG code is available at https://github.com/FERMat-ML/OMatG.

cs.LG↗

arXiv2024

The need to implement FAIR principles in biomolecular simulations

This letter illustrates the opinion of the molecular dynamics (MD) community on the need to adopt a new FAIR paradigm for the use of molecular simulations. It highlights the necessity of a collaborative effort to create, establish, and sustain a database that allows findability, accessibility, interoperability, and reusability of molecular dynamics simulation data. Such a development would democratize the field and significantly improve the impact of MD simulations on life science research. This will transform our working paradigm, pushing the field to a new frontier. We invite you to support our initiative at the MDDB community (https://mddbr.eu/community/) Now published as: Amaro, R.E., et al. The need to implement FAIR principles in biomolecular simulations. Nat Methods (2025) https://doi.org/10.1038/s41592-025-02635-0

q-bio.BM↗

arXiv2024

Guided Multi-objective Generative AI to Enhance Structure-based Drug Design

Generative AI has the potential to revolutionize drug discovery. Yet, despite recent advances in deep learning, existing models cannot generate molecules that satisfy all desired physicochemical properties. Herein, we describe IDOLpro, a generative chemistry AI combining diffusion with multi-objective optimization for structure-based drug design. Differentiable scoring functions guide the latent variables of the diffusion model to explore uncharted chemical space and generate novel ligands in silico, optimizing a plurality of target physicochemical properties. We demonstrate our platform's effectiveness by generating ligands with optimized binding affinity and synthetic accessibility on two benchmark sets. IDOLpro produces ligands with binding affinities over 10%-20% better than the next best state-of-the-art method on each test set, producing more drug-like molecules with generally better synthetic accessibility scores than other methods. We do a head-to-head comparison of IDOLpro against a classic virtual screen of a large database of drug-like molecules. We show that IDOLpro can generate molecules for a range of important disease-related targets with better binding affinity and synthetic accessibility than any molecule found in the virtual screen while being over 100x faster and less expensive to run. On a test set of experimental complexes, IDOLpro is the first to produce molecules with better binding affinities than experimentally observed ligands. IDOLpro can accommodate other scoring functions (e.g. ADME-Tox) to accelerate hit-finding, hit-to-lead, and lead optimization for drug discovery.

physics.chem-ph↗

arXiv2023

Accelerated Organic Crystal Structure Prediction with Genetic Algorithms and Machine Learning

We present a high-throughput, end-to-end pipeline for organic crystal structure prediction (CSP) -- the problem of identifying the stable crystal structures that will form from a given molecule based only on its molecular composition. Our tool uses Neural Network Potentials (NNPs) to allow for efficient screening and structural relaxations of generated crystal candidates. Our pipeline consists of two distinct stages -- random search, whereby crystal candidates are randomly generated and screened, and optimization, where a genetic algorithm (GA) optimizes this screened population. We assess the performance of each stage of our pipeline on 21 molecules taken from the Cambridge Crystallographic Data Centre's CSP blind tests. We show that random search alone yields matches for $\approx 50\%$ of targets. We then validate the potential of our full pipeline, making use of the GA to optimize the Root Mean-Squared Deviation (RMSD) between crystal candidates and the experimentally derived structure. With this approach, we are able to find matches for $\approx80\%$ of candidates with 10-100 times smaller initial population sizes than when using random search. Lastly, we run our full pipeline with an ANI model that is trained on a small dataset of molecules extracted from crystal structures in the Cambridge Structural Database, generating $\approx 60\%$ of targets. By leveraging ML models trained to predict energies at the DFT level, our pipeline has the potential to approach the accuracy of \emph{ab initio} methods and the efficiency of empirical force-fields.

cond-mat.mtrl-sci↗

arXiv2018

Transferable Molecular Charge Assignment Using Deep Neural Networks

We use HIP-NN, a neural network architecture that excels at predicting molecular energies, to predict atomic charges. The charge predictions are accurate over a wide range of molecules (both small and large) and for a diverse set of charge assignment schemes. To demonstrate the power of charge prediction on non-equilibrium geometries, we use HIP-NN to generate IR spectra from dynamical trajectories on a variety of molecules. The results are in good agreement with reference IR spectra produced by traditional theoretical methods. Critically, for this application, HIP-NN charge predictions are about 104 times faster than direct DFT charge calculations. Thus, ML provides a pathway to greatly increase the range of feasible simulations while retaining quantum-level accuracy. In summary, our results provide further evidence that machine learning can replicate high-level quantum calculations at a tiny fraction of the computational cost.

physics.chem-ph↗