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Coarse-grained (CG) molecular simulations have become a standard tool to study molecular processes on time- and length-scales inaccessible to all-atom simulations. Parameterizing CG force fields to match all-atom simulations has mainly…

Computational Physics · Physics 2023-02-07 Jonas Köhler , Yaoyi Chen , Andreas Krämer , Cecilia Clementi , Frank Noé

Deep generative models that produce novel molecular structures have the potential to facilitate chemical discovery. Flow matching is a recently proposed generative modeling framework that has achieved impressive performance on a variety of…

Machine Learning · Computer Science 2024-11-26 Ian Dunn , David R. Koes

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…

Machine Learning · Computer Science 2025-02-19 Joonyoung F. Joung , Mun Hong Fong , Nicholas Casetti , Jordan P. Liles , Ne S. Dassanayake , Connor W. Coley

Conformational isomers or conformers of molecules play a decisive role in chemistry and biology. However, experimental methods to investigate chemical reaction dynamics are typically not conformer-sensitive. Here, we report on a gas-phase…

We propose a framework using normalizing-flow based models, SELF-Referencing Embedded Strings, and multi-objective optimization that efficiently generates small molecules. With an initial training set of only 100 small molecules, FastFlows…

Chemical Physics · Physics 2022-02-01 Nathan C. Frey , Vijay Gadepally , Bharath Ramsundar

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…

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative…

Biological Physics · Physics 2025-03-05 Yaowei Jin , Qi Huang , Ziyang Song , Mingyue Zheng , Dan Teng , Qian Shi

Chemically-responsive polymers are macromolecules that respond to local variations of the chemical composition of the solution by changing their conformation, with notable examples including polyelectrolytes, proteins and DNA. The polymer…

Soft Condensed Matter · Physics 2022-07-27 Marco De Corato , Marino Arroyo

Structure-based drug design (SBDD), aiming to generate 3D molecules with high binding affinity toward target proteins, is a vital approach in novel drug discovery. Although recent generative models have shown great potential, they suffer…

Machine Learning · Computer Science 2025-11-05 Jingyuan Zhou , Hao Qian , Shikui Tu , Lei Xu

Generative models coupled with reinforcement learning (RL), such as REINVENT and PepINVENT, have emerged as a powerful framework for de novo molecular design. During the ideation process these generative frameworks utilize various…

Artificial Intelligence · Computer Science 2026-05-08 Laura van Weesep , Sunay Chankeshwara , Leonardo De Maria , Florian David , Ola Engkvist , Gökçe Geylan

Exploring molecular energy landscapes and identifying ground-state conformations are central challenges in computational chemistry. However, generating diverse low-energy conformers from molecular graphs remains expensive with traditional…

Machine Learning · Computer Science 2026-05-25 Guikun Xu , Xiaohan Yi , Ziqiao Meng , Peilin Zhao , Yatao Bian

Generating new molecules is fundamental to advancing critical applications such as drug discovery and material synthesis. Flows can generate molecules effectively by inverting the encoding process, however, existing flow models either…

Machine Learning · Computer Science 2022-10-14 Yogesh Verma , Samuel Kaski , Markus Heinonen , Vikas Garg

Macrocyclic peptides are an emerging therapeutic modality, yet computational approaches for accurately sampling their diverse 3D ensembles remain challenging due to their conformational diversity and geometric constraints. Here, we…

Biomolecules · Quantitative Biology 2024-08-15 Colin A. Grambow , Hayley Weir , Nathaniel L. Diamant , Gabriele Scalia , Tommaso Biancalani , Kangway V. Chuang

Therapeutic peptides show promise in targeting previously undruggable binding sites, with recent advancements in deep generative models enabling full-atom peptide co-design for specific protein receptors. However, the critical role of…

Machine Learning · Computer Science 2026-01-09 Fang Wu , Zhengyuan Zhou , Shuting Jin , Xiangxiang Zeng , Jure Leskovec , Jinbo Xu

Over the past decade, advances in generative modeling, such as generative adversarial networks, masked autoencoders, and diffusion models, have significantly transformed biological research and discovery, enabling breakthroughs in molecule…

Machine Learning · Computer Science 2026-03-10 Zihao Li , Zhichen Zeng , Xiao Lin , Feihao Fang , Yanru Qu , Zhe Xu , Zhining Liu , Xuying Ning , Tianxin Wei , Ge Liu , Hanghang Tong , Jingrui He

Designing ligand-binding proteins, such as enzymes and biosensors, is essential in bioengineering and protein biology. One critical step in this process involves designing protein pockets, the protein interface binding with the ligand.…

Biomolecules · Quantitative Biology 2024-10-01 Zaixi Zhang , Marinka Zitnik , Qi Liu

Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first…

Biomolecules · Quantitative Biology 2024-06-04 Jiahan Li , Chaoran Cheng , Zuofan Wu , Ruihan Guo , Shitong Luo , Zhizhou Ren , Jian Peng , Jianzhu Ma

Molecular conformer generation is a fundamental task in computational chemistry. Several machine learning approaches have been developed, but none have outperformed state-of-the-art cheminformatics methods. We propose torsional diffusion, a…

Chemical Physics · Physics 2023-03-02 Bowen Jing , Gabriele Corso , Jeffrey Chang , Regina Barzilay , Tommi Jaakkola

Generating molecular graphs with desired chemical properties driven by deep graph generative models provides a very promising way to accelerate drug discovery process. Such graph generative models usually consist of two steps: learning…

Machine Learning · Statistics 2020-06-19 Chengxi Zang , Fei Wang

Recent advancements in deep learning-based modeling of molecules promise to accelerate in silico drug discovery. A plethora of generative models is available, building molecules either atom-by-atom and bond-by-bond or fragment-by-fragment.…