Symmetry-Constrained Generation of Diverse Low-Bandgap Molecules with Monte Carlo Tree Search

Organic optoelectronic materials are a promising avenue for next-generation electronic devices due to their solution processability, mechanical flexibility, and tunable electronic properties. In particular, near-infrared (NIR) sensitive molecules have unique applications in night-vision equipment and biomedical imaging. Molecular engineering has played a crucial role in developing non-fullerene acceptors (NFAs) such as the Y-series molecules, which have significantly improved the power conversion efficiency (PCE) of solar cells and enhanced spectral coverage in the NIR region. However, systematically designing molecules with targeted optoelectronic properties while ensuring synthetic accessibility remains a challenge. To address this, we leverage structural priors from domain-focused, patent-mined datasets of organic electronic molecules using a symmetry-aware fragment decomposition algorithm and a fragment-constrained Monte Carlo Tree Search (MCTS) generator. Our approach generates candidates that retain symmetry constraints from the patent dataset, while also exhibiting red-shifted absorption, as validated by TD-DFT calculations.

Efficient Generation of Molecular Clusters with Dual-Scale Equivariant Flow Matching

Amorphous molecular solids offer a promising alternative to inorganic semiconductors, owing to their mechanical flexibility and solution processability. The packing structure of these materials plays a crucial role in determining their electronic and transport properties, which are key to enhancing the efficiency of devices like organic solar cells (OSCs). However, obtaining these optoelectronic properties computationally requires molecular dynamics (MD) simulations to generate a conformational ensemble, a process that can be computationally expensive due to the large system sizes involved. Recent advances have focused on using generative models, particularly flow-based models as Boltzmann generators, to improve the efficiency of MD sampling. In this work, we developed a dual-scale flow matching method that separates training and inference into coarse-grained and all-atom stages and enhances both the accuracy and efficiency of standard flow matching samplers. We demonstrate the effectiveness of this method on a dataset of Y6 molecular clusters obtained through MD simulations, and we benchmark its efficiency and accuracy against single-scale flow matching methods.

Think While You Generate: Discrete Diffusion with Planned Denoising

Discrete diffusion has achieved state-of-the-art performance, outperforming or approaching autoregressive models on standard benchmarks. In this work, we introduce Discrete Diffusion with Planned Denoising (DDPD), a novel framework that separates the generation process into two models: a planner and a denoiser. At inference time, the planner selects which positions to denoise next by identifying the most corrupted positions in need of denoising, including both initially corrupted and those requiring additional refinement. This plan-and-denoise approach enables more efficient reconstruction during generation by iteratively identifying and denoising corruptions in the optimal order. DDPD outperforms traditional denoiser-only mask diffusion methods, achieving superior results on language modeling benchmarks such as text8, OpenWebText, and token-based generation on ImageNet $256 \times 256$. Notably, in language modeling, DDPD significantly reduces the performance gap between diffusion-based and autoregressive methods in terms of generative perplexity. Code is available at https://github.com/liusulin/DDPD.

Flow Matching for Accelerated Simulation of Atomic Transport in Materials

We introduce LiFlow, a generative framework to accelerate molecular dynamics (MD) simulations for crystalline materials that formulates the task as conditional generation of atomic displacements. The model uses flow matching, with a Propagator submodel to generate atomic displacements and a Corrector to locally correct unphysical geometries, and incorporates an adaptive prior based on the Maxwell-Boltzmann distribution to account for chemical and thermal conditions. We benchmark LiFlow on a dataset comprising 25-ps trajectories of lithium diffusion across 4,186 solid-state electrolyte (SSE) candidates at four temperatures. The model obtains a consistent Spearman rank correlation of 0.7-0.8 for lithium mean squared displacement (MSD) predictions on unseen compositions. Furthermore, LiFlow generalizes from short training trajectories to larger supercells and longer simulations while maintaining high accuracy. With speed-ups of up to 600,000$\times$ compared to first-principles methods, LiFlow enables scalable simulations at significantly larger length and time scales.

Learning Ordering in Crystalline Materials with Symmetry-Aware Graph Neural Networks

Graph convolutional neural networks (GCNNs) have become a machine learning workhorse for screening the chemical space of crystalline materials in fields such as catalysis and energy storage, by predicting properties from structures. Multicomponent materials, however, present a unique challenge since they can exhibit chemical (dis)order, where a given lattice structure can encompass a variety of elemental arrangements ranging from highly ordered structures to fully disordered solid solutions. Critically, properties like stability, strength, and catalytic performance depend not only on structures but also on orderings. To enable rigorous materials design, it is thus critical to ensure GCNNs are capable of distinguishing among atomic orderings. However, the ordering-aware capability of GCNNs has been poorly understood. Here, we benchmark various neural network architectures for capturing the ordering-dependent energetics of multicomponent materials in a custom-made dataset generated with high-throughput atomistic simulations. Conventional symmetry-invariant GCNNs were found unable to discern the structural difference between the diverse symmetrically inequivalent atomic orderings of the same material, while symmetry-equivariant model architectures could inherently preserve and differentiate the distinct crystallographic symmetries of various orderings.

Interpolation and differentiation of alchemical degrees of freedom in machine learning interatomic potentials

Machine learning interatomic potentials (MLIPs) have become a workhorse of modern atomistic simulations, and recently published universal MLIPs, pre-trained on large datasets, have demonstrated remarkable accuracy and generalizability. However, the computational cost of MLIPs limits their applicability to chemically disordered systems requiring large simulation cells or to sample-intensive statistical methods. Here, we report the use of continuous and differentiable alchemical degrees of freedom in atomistic materials simulations, exploiting the fact that graph neural network MLIPs represent discrete elements as real-valued tensors. The proposed method introduces alchemical atoms with corresponding weights into the input graph, alongside modifications to the message-passing and readout mechanisms of MLIPs, and allows smooth interpolation between the compositional states of materials. The end-to-end differentiability of MLIPs enables efficient calculation of the gradient of energy with respect to the compositional weights. Leveraging these gradients, we propose methodologies for optimizing the composition of solid solutions towards target macroscopic properties and conducting alchemical free energy simulations to quantify the free energy of vacancy formation and composition changes. The approach offers an avenue for extending the capabilities of universal MLIPs in the modeling of compositional disorder and characterizing the phase stabilities of complex materials systems.

Learning Collective Variables for Protein Folding with Labeled Data Augmentation through Geodesic Interpolation

In molecular dynamics (MD) simulations, rare events, such as protein folding, are typically studied by means of enhanced sampling techniques, most of which rely on the definition of a collective variable (CV) along which the acceleration occurs. Obtaining an expressive CV is crucial, but often hindered by the lack of information about the particular event, e.g., the transition from unfolded to folded conformation. We propose a simulation-free data augmentation strategy using physics-inspired metrics to generate geodesic interpolations resembling protein folding transitions, thereby improving sampling efficiency without true transition state samples. Leveraging interpolation progress parameters, we introduce a regression-based learning scheme for CV models, which outperforms classifier-based methods when transition state data is limited and noisy

Machine-learning-accelerated simulations enable heuristic-free surface reconstruction

Understanding material surfaces and interfaces is vital in applications like catalysis or electronics. Ab initio simulations, combining energies from electronic structure with statistical mechanics, can, in principle, predict the structure of material surfaces as a function of thermodynamic variables. However, accurate energy simulations are prohibitive when coupled to the vast phase space that must be statistically sampled. Here, we present a bi-faceted computational loop to predict surface phase diagrams of multi-component materials that accelerates both the energy scoring and statistical sampling methods. Fast, scalable, and data-efficient machine learning interatomic potentials are trained on high-throughput density-functional theory calculations through closed-loop active learning. Markov-chain Monte Carlo sampling in the semi-grand canonical ensemble is enabled by using virtual surface sites. The predicted surfaces for GaN(0001) and SrTiO3(001) are in agreement with past work and suggest that the proposed strategy can model complex material surfaces and discover previously unreported surface terminations.

Single-model uncertainty quantification in neural network potentials does not consistently outperform model ensembles

Neural networks (NNs) often assign high confidence to their predictions, even for points far out-of-distribution, making uncertainty quantification (UQ) a challenge. When they are employed to model interatomic potentials in materials systems, this problem leads to unphysical structures that disrupt simulations, or to biased statistics and dynamics that do not reflect the true physics. Differentiable UQ techniques can find new informative data and drive active learning loops for robust potentials. However, a variety of UQ techniques, including newly developed ones, exist for atomistic simulations and there are no clear guidelines for which are most effective or suitable for a given case. In this work, we examine multiple UQ schemes for improving the robustness of NN interatomic potentials (NNIPs) through active learning. In particular, we compare incumbent ensemble-based methods against strategies that use single, deterministic NNs: mean-variance estimation, deep evidential regression, and Gaussian mixture models. We explore three datasets ranging from in-domain interpolative learning to more extrapolative out-of-domain generalization challenges: rMD17, ammonia inversion, and bulk silica glass. Performance is measured across multiple metrics relating model error to uncertainty. Our experiments show that none of the methods consistently outperformed each other across the various metrics. Ensembling remained better at generalization and for NNIP robustness; MVE only proved effective for in-domain interpolation, while GMM was better out-of-domain; and evidential regression, despite its promise, was not the preferable alternative in any of the cases. More broadly, cost-effective, single deterministic models cannot yet consistently match or outperform ensembling for uncertainty quantification in NNIPs.

Automated patent extraction powers generative modeling in focused chemical spaces

Deep generative models have emerged as an exciting avenue for inverse molecular design, with progress coming from the interplay between training algorithms and molecular representations. One of the key challenges in their applicability to materials science and chemistry has been the lack of access to sizeable training datasets with property labels. Published patents contain the first disclosure of new materials prior to their publication in journals, and are a vast source of scientific knowledge that has remained relatively untapped in the field of data-driven molecular design. Because patents are filed seeking to protect specific uses, molecules in patents can be considered to be weakly labeled into application classes. Furthermore, patents published by the US Patent and Trademark Office (USPTO) are downloadable and have machine-readable text and molecular structures. In this work, we train domain-specific generative models using patent data sources by developing an automated pipeline to go from USPTO patent digital files to the generation of novel candidates with minimal human intervention. We test the approach on two in-class extracted datasets, one in organic electronics and another in tyrosine kinase inhibitors. We then evaluate the ability of generative models trained on these in-class datasets on two categories of tasks (distribution learning and property optimization), identify strengths and limitations, and suggest possible explanations and remedies that could be used to overcome these in practice.