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Protein structure prediction is a critical and longstanding challenge in biology, garnering widespread interest due to its significance in understanding biological processes. A particular area of focus is the prediction of missing loops in…

Small-molecule foundation models are typically pretrained on standalone molecular data, unlike vision and language models that often benefit from cross-modal or relational supervision. Protein-ligand co-folding provides a molecular analogue…

Biomolecules · Quantitative Biology 2026-05-25 Hyosoon Jang , Hyunjin Seo , Honghui Kim , Seonghyun Park , Taewon Kim , Yunhui Jang , Sungsoo Ahn

The Boltzmann distribution of a protein provides a roadmap to all of its functional states. Normalizing flows are a promising tool for modeling this distribution, but current methods are intractable for typical pharmacological targets; they…

Machine Learning · Computer Science 2024-01-10 Joseph C. Kim , David Bloore , Karan Kapoor , Jun Feng , Ming-Hong Hao , Mengdi Wang

Protein folding is the intricate process by which a linear sequence of amino acids self-assembles into a unique three-dimensional structure. Protein folding kinetics is the study of pathways and time-dependent mechanisms a protein undergoes…

Machine Learning · Computer Science 2023-09-19 Vijay Arvind. R , Haribharathi Sivakumar , Brindha. R

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

Simulations of biological macromolecules play an important role in understanding the physical basis of a number of complex processes such as protein folding. Even with increasing computational power and evolution of specialized…

Distributed, Parallel, and Cluster Computing · Computer Science 2019-09-18 Hyungro Lee , Heng Ma , Matteo Turilli , Debsindhu Bhowmik , Shantenu Jha , Arvind Ramanathan

Flow-matching models provide a powerful framework for various applications, offering efficient sampling and flexible probability path modeling. These models are characterized by flows with low curvature in learned generative trajectories,…

Machine Learning · Computer Science 2025-01-22 Zibin Wang , Zhiyuan Ouyang , Xiangyun Zhang

Designing novel proteins with desired functions is crucial in biology and chemistry. However, most existing work focus on protein sequence design, leaving protein sequence and structure co-design underexplored. In this paper, we propose…

Machine Learning · Computer Science 2023-10-05 Zhenqiao Song , Yunlong Zhao , Yufei Song , Wenxian Shi , Yang Yang , Lei Li

We present BioLangFusion, a simple approach for integrating pre-trained DNA, mRNA, and protein language models into unified molecular representations. Motivated by the central dogma of molecular biology (information flow from gene to…

Machine Learning · Computer Science 2025-06-11 Amina Mollaysa , Artem Moskale , Pushpak Pati , Tommaso Mansi , Mangal Prakash , Rui Liao

Inferring the structural properties of a protein from its amino acid sequence is a challenging yet important problem in biology. Structures are not known for the vast majority of protein sequences, but structure is critical for…

Machine Learning · Computer Science 2019-10-17 Tristan Bepler , Bonnie Berger

Designing novel functional proteins crucially depends on accurately modeling their fitness landscape. Given the limited availability of functional annotations from wet-lab experiments, previous methods have primarily relied on…

Machine Learning · Computer Science 2024-12-03 Zuobai Zhang , Pascal Notin , Yining Huang , Aurélie Lozano , Vijil Chenthamarakshan , Debora Marks , Payel Das , Jian Tang

Deep generative models that learn from the distribution of natural protein sequences and structures may enable the design of new proteins with valuable functions. While the majority of today's models focus on generating either sequences or…

Biomolecules · Quantitative Biology 2024-10-03 Chentong Wang , Sarah Alamdari , Carles Domingo-Enrich , Ava Amini , Kevin K. Yang

Modeling biological sequences such as DNA, RNA, and proteins is crucial for understanding complex processes like gene regulation and protein synthesis. However, most current models either focus on a single type or treat multiple types of…

Genomics · Quantitative Biology 2024-10-16 Weixi Xiang , Xueting Han , Xiujuan Chai , Jing Bai

Understanding protein dynamics is critical for elucidating their biological functions. The increasing availability of molecular dynamics (MD) data enables the training of deep generative models to efficiently explore the conformational…

Machine Learning · Computer Science 2025-12-04 Yuning Shen , Lihao Wang , Huizhuo Yuan , Yan Wang , Bangji Yang , Quanquan Gu

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has…

Computation and Language · Computer Science 2025-05-20 Yanting Li , Jiyue Jiang , Zikang Wang , Ziqian Lin , Dongchen He , Yuheng Shan , Yanruisheng Shao , Jiayi Li , Xiangyu Shi , Jiuming Wang , Yanyu Chen , Yimin Fan , Han Li , Yu Li

Generating molecular graphs is crucial in drug design and discovery but remains challenging due to the complex interdependencies between nodes and edges. While diffusion models have demonstrated their potentiality in molecular graph design,…

Machine Learning · Computer Science 2024-11-11 Xiaoyang Hou , Tian Zhu , Milong Ren , Dongbo Bu , Xin Gao , Chunming Zhang , Shiwei Sun

Predicting low-energy molecular conformations given a molecular graph is an important but challenging task in computational drug discovery. Existing state-of-the-art approaches either resort to large scale transformer-based models that…

Quantitative Methods · Quantitative Biology 2024-10-31 Majdi Hassan , Nikhil Shenoy , Jungyoon Lee , Hannes Stark , Stephan Thaler , Dominique Beaini

Protein engineering is experiencing a paradigmatic shift through the integration of geometric deep learning into computational design workflows. While traditional strategies, such as rational design and directed evolution, have enabled…

Existing rectified flow models are based on linear trajectories between data and noise distributions. This linearity enforces zero curvature, which can inadvertently force the image generation process through low-probability regions of the…

Computer Vision and Pattern Recognition · Computer Science 2025-08-26 Yan Luo , Drake Du , Hao Huang , Yi Fang , Mengyu Wang

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but often lack the structural knowledge essential for some biological applications. To address this, we introduce a method to…

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