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The diverse nature of protein prediction tasks has traditionally necessitated specialized models, hindering the development of broadly applicable and computationally efficient Protein Language Models (PLMs). In this work, we introduce…

Proteins play a critical role in carrying out biological functions, and their 3D structures are essential in determining their functions. Accurately predicting the conformation of protein side-chains given their backbones is important for…

Quantitative Methods · Quantitative Biology 2024-02-19 Yangtian Zhang , Zuobai Zhang , Bozitao Zhong , Sanchit Misra , Jian Tang

The development of therapeutic antibodies heavily relies on accurate predictions of how antigens will interact with antibodies. Existing computational methods in antibody design often overlook crucial conformational changes that antigens…

Quantitative Methods · Quantitative Biology 2025-03-05 Cheng Tan , Yijie Zhang , Zhangyang Gao , Yufei Huang , Haitao Lin , Lirong Wu , Fandi Wu , Mathieu Blanchette , Stan. Z. Li

Large-scale Protein Language Models (PLMs) have improved performance in protein prediction tasks, ranging from 3D structure prediction to various function predictions. In particular, AlphaFold, a ground-breaking AI system, could potentially…

Quantitative Methods · Quantitative Biology 2022-10-18 Mingyang Hu , Fajie Yuan , Kevin K. Yang , Fusong Ju , Jin Su , Hui Wang , Fei Yang , Qiuyang Ding

The function of biomolecules such as proteins depends on their ability to interconvert between a wide range of structures or "conformations." Researchers have endeavored for decades to develop computational methods to predict the…

Biomolecules · Quantitative Biology 2026-02-05 Daniel D. Richman , Jessica Karaguesian , Carl-Mikael Suomivuori , Ron O. Dror

Existing state-of-the-art methods that take a single RNA sequence and predict the corresponding RNA secondary-structure are thermodynamic methods. These predict the most stable RNA structure, but do not consider the process of structure…

Biomolecules · Quantitative Biology 2012-07-26 Jeff R. Proctor , Irmtraud M. Meyer

A reliable prediction of 3D protein structures from sequence data remains a big challenge due to both theoretical and computational difficulties. We have previously shown that our kinetostatic compliance method (KCM) implemented into the…

Computational Engineering, Finance, and Science · Computer Science 2017-12-27 Pouya Tavousi , Morad Behandish , Horea T. Ilies , Kazem Kazerounian

The effects of ligand binding on protein structures and their in vivo functions carry numerous implications for modern biomedical research and biotechnology development efforts such as drug discovery. Although several deep learning (DL)…

Machine Learning · Computer Science 2026-03-24 Alex Morehead , Nabin Giri , Jian Liu , Pawan Neupane , Jianlin Cheng

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

Due to the hierarchical organization of RNA structures and their pivotal roles in fulfilling RNA functions, the formation of RNA secondary structure critically influences many biological processes and has thus been a crucial research topic.…

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the…

Biological Physics · Physics 2008-11-24 Pablo Echenique

The accurate prediction of protein-RNA binding affinity remains an unsolved problem in structural biology, limiting opportunities in understanding gene regulation and designing RNA-targeting therapeutics. A central obstacle is the…

The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…

Statistical Mechanics · Physics 2009-10-31 Chao Tang

Proteins are miniature machines whose function depends on their three-dimensional (3D) structure. Determining this structure computationally remains an unsolved grand challenge. A major bottleneck involves selecting the most accurate…

Quantitative Methods · Quantitative Biology 2020-11-30 Stephan Eismann , Patricia Suriana , Bowen Jing , Raphael J. L. Townshend , Ron O. Dror

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

Protein structure prediction has reached revolutionary levels of accuracy on single structures, yet distributional modeling paradigms are needed to capture the conformational ensembles and flexibility that underlie biological function.…

Biomolecules · Quantitative Biology 2023-04-06 Bowen Jing , Ezra Erives , Peter Pao-Huang , Gabriele Corso , Bonnie Berger , Tommi Jaakkola

Recent advancements in deep learning for predicting 3D protein structures have shown promise, particularly when leveraging inputs like protein sequences and Cryo-Electron microscopy (Cryo-EM) images. However, these techniques often fall…

Computer Vision and Pattern Recognition · Computer Science 2024-08-13 Jaydeep Rade , Ethan Herron , Soumik Sarkar , Anwesha Sarkar , Adarsh Krishnamurthy

Multiple Sequence Alignment (MSA) plays a pivotal role in unveiling the evolutionary trajectories of protein families. The accuracy of protein structure predictions is often compromised for protein sequences that lack sufficient homologous…

Biomolecules · Quantitative Biology 2024-10-29 Bo Chen , Zhilei Bei , Xingyi Cheng , Pan Li , Jie Tang , Le Song

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

Structure determination is key to understanding protein function at a molecular level. Whilst significant advances have been made in predicting structure and function from amino acid sequence, researchers must still rely on expensive,…

Computer Vision and Pattern Recognition · Computer Science 2020-09-01 Alexander Hudson , Shaogang Gong