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, we present 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.

Accelerating inverse design of crystalline materials with generative models has significant implications for a range of technologies. Unlike other atomic systems, 3D crystals are invariant to discrete groups of isometries called the space groups. Crucially, these space group symmetries are known to heavily influence materials properties. We propose SGEquiDiff, a crystal generative model which naturally handles space group constraints with space group invariant likelihoods. SGEquiDiff consists of an SE(3)-invariant, telescoping discrete sampler of crystal lattices; permutation-invariant, transformer-based autoregressive sampling of Wyckoff positions, elements, and numbers of symmetrically unique atoms; and space group equivariant diffusion of atomic coordinates. We show that space group equivariant vector fields automatically live in the tangent spaces of the Wyckoff positions. SGEquiDiff achieves state-of-the-art performance on standard benchmark datasets as assessed by quantitative proxy metrics and quantum mechanical calculations.

Coordinate denoising has emerged as a promising method for 3D molecular pretraining due to its theoretical connection to learning a molecular force field. However, existing denoising methods rely on oversimplified molecular dynamics that assume atomic motions to be isotropic and homoscedastic.

Predicting the 3D conformation of small molecules within protein binding sites is a key challenge in drug design. When a crystallized reference ligand (template) is available, it provides geometric priors that can guide 3D pose prediction. We present a two-stage method for ligand conformation generation guided by such templates. In the first stage, we introduce a molecular alignment approach based on flow-matching to generate 3D coordinates for the ligand, using the template structure as a reference. In the second stage, a differentiable pose optimization procedure refines this conformation based on shape and pharmacophore similarities, internal energy, and, optionally, the protein binding pocket. We introduce a new benchmark of ligand pairs co-crystallized with the same target to evaluate our approach and show that it outperforms standard docking tools and open-access alignment methods, especially in cases involving low similarity to the template or high ligand flexibility.

The integration of logic programs with embedding models resulted in a class of neurosymbolic frameworks that jointly learn symbolic rules and representations for the symbols in the logic (constant or predicate). The key idea that enabled this integration was the differentiable relaxation of unification, the algorithm for variable instantiation during inference in logic programs. Unlike unification, its relaxed counterpart exploits the similarity between symbols in the embedding space to decide when two symbols are semantically equivalent. We show that this similarity between symbols violates the transitive law of equivalence, leading to undesirable side effects in learning and inference. To alleviate those side effects, we are the first to revamp the well-known possible world semantics of probabilistic logic programs into new semantics called equivalence semantics. In our semantics, a probabilistic logic program induces a probability distribution over all possible equivalence relations between symbols, instead of a probability distribution over all possible subsets of probabilistic facts. We propose a factorization of the equivalence distribution using latent random variables and characterize its expressivity. Additionally, we propose both exact and approximate techniques for reasoning in our semantics. Experiments on well-known benchmarks show that the equivalence semantics leads to neurosymbolic models with up to 42% higher results than state-of-the-art baselines.

Cyclic peptides exhibit better binding affinity and proteolytic stability compared to their linear counterparts. However, the development of cyclic peptide design models is hindered by the scarcity of data. To address this, we introduce CPSea(Cyclic Peptide Sea), a dataset of 2.71 million cyclic peptide-receptor complexes, curated through systematic mining of the AlphaFold Database (AFDB). Our pipeline extracts compact domains from AFDB, identifies cyclization sites using the β-carbon (Cβ) distance thresholds, and applies multi-stage filtering to ensure structure fidelity and binding compatibility. Compared with experimental data of cyclic peptides, CPSea shows similar distributions in metrics on structure fidelity and wet-lab compatibility. To our knowledge, CPSea is the largest cyclic peptide-receptor dataset to date, enabling end-to-end model training for the first time.

Tthesehe challenges, we introduce cKnoarbwMol-100K,oxylate group and the polarizable sulfur atom, methylsulfanyl group attaalarchge-scaed tole tdatasethe sixwithth c100Karbofine-grainedn and molecular annotations Theacross polamriultiplety of the molecule is increased by the polar verum with data available.

Crystal structures are defined by the periodic arrangement of atoms in 3D space, inherently making them equivariant to SO(3) group. A fundamental requirement for crystal property prediction is that the model's output should remain invariant to arbitrary rotational transformations of the input structure. One promising strategy to achieve this invariance is to align the given crystal structure into a canonical orientation with appropriately computed rotations, or called frames. However, existing work either only considers a global frame or solely relies on more advanced local frames based on atoms' local structure. A global frame is too coarse to capture the local structure heterogeneity of the crystal, while local frames may inadvertently disrupt crystal symmetry, limiting their expressivity. In this work, we revisit the frame design problem for crystalline materials and propose a novel approach to construct expressive Symmetry-Preserving Frames, dubbed as SPFrame, for modeling crystal structures.

Molecular Relational Learning (MRL) is a rapidly growing field that focuses on understanding the interaction dynamics between molecules, which is crucial for applications ranging from catalyst engineering to drug discovery. Despite recent progress, ture of molecules, earlier MRL as obtaining approaches the are 3D limited interaction to using geometry only the remains 2D topological prohibiti strucvely expensive. This paper introduces a novel 3D geometric pre-training strategy for MRL (3DMRL) that incorporates a 3D virtual interaction environment, overcoming the the constructe limitations d of 3D costly virtual tradit interaction ional quantum environment, mechanical 3DMRL calculation trains 2D methods. MRL model With to learn the global and local 3D geometric information of molecular interaction. Extensive experiments on various tasks using real-world datasets, including out-ofdistribution and extrapolation scenarios, demonstrate the effectiveness of 3DMRL, sho publicly wing a up vailable to a 24.93% at https://github.com/

Understanding molecules is key to understanding organisms and driving advances in drug discovery, requiring interdisciplinary knowledge across chemistry and biology. Although large molecular language models have achieved notable success in task transfer, they often struggle to accurately analyze molecular features due to limited knowledge and reasoning capabilities. To address this issue, we present Mol-LLaMA, a large molecular language model that grasps the general knowledge centered on molecules and exhibits explainability and reasoning ability. To this end, we design key data types that encompass the fundamental molecular features, taking into account the essential abilities for molecular reasoning. Further, to improve molecular understanding, we propose a module that integrates complementary information from different molecular encoders, leveraging the distinct advantages of molecular representations. Our experimental results demonstrate that Mol-LLaMA is capable of comprehending the general features of molecules and providing informative responses, implying its potential as a general-purpose assistant for molecular analysis. Our project page is at https://mol-llama.github.io/.