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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

Protein structure prediction is pivotal for understanding the structure-function relationship of proteins, advancing biological research, and facilitating pharmaceutical development and experimental design. While deep learning methods and…

Machine Learning · Computer Science 2024-12-30 Kaihui Cheng , Ce Liu , Qingkun Su , Jun Wang , Liwei Zhang , Yining Tang , Yao Yao , Siyu Zhu , Yuan Qi

Protein-protein bindings play a key role in a variety of fundamental biological processes, and thus predicting the effects of amino acid mutations on protein-protein binding is crucial. To tackle the scarcity of annotated mutation data,…

Quantitative Methods · Quantitative Biology 2024-05-20 Lirong Wu , Yijun Tian , Haitao Lin , Yufei Huang , Siyuan Li , Nitesh V Chawla , Stan Z. Li

Designing protein-binding proteins with high affinity is critical in biomedical research and biotechnology. Despite recent advancements targeting specific proteins, the ability to create high-affinity binders for arbitrary protein targets…

Machine Learning · Computer Science 2025-11-03 Zhenqiao Song , Tiaoxiao Li , Lei Li , Martin Renqiang Min

Designing protein sequences with specific biological functions and structural stability is crucial in biology and chemistry. Generative models already demonstrated their capabilities for reliable protein design. However, previous models are…

Machine Learning · Computer Science 2024-02-28 Lin Zongying , Li Hao , Lv Liuzhenghao , Lin Bin , Zhang Junwu , Chen Calvin Yu-Chian , Yuan Li , Tian Yonghong

Structure-based drug design (SBDD) aims to generate 3D ligand molecules that bind to specific protein targets. Existing 3D deep generative models including diffusion models have shown great promise for SBDD. However, it is complex to…

Biomolecules · Quantitative Biology 2024-03-01 Zhilin Huang , Ling Yang , Zaixi Zhang , Xiangxin Zhou , Yu Bao , Xiawu Zheng , Yuwei Yang , Yu Wang , Wenming Yang

The conformational landscape of proteins is crucial to understanding their functionality in complex biological processes. Traditional physics-based computational methods, such as molecular dynamics (MD) simulations, suffer from rare event…

Biomolecules · Quantitative Biology 2024-09-25 Yan Wang , Lihao Wang , Yuning Shen , Yiqun Wang , Huizhuo Yuan , Yue Wu , Quanquan Gu

AI-assisted protein design has emerged as a critical tool for advancing biotechnology, as deep generative models have demonstrated their reliability in this domain. However, most existing models primarily utilize protein sequence or…

Computational Engineering, Finance, and Science · Computer Science 2026-05-27 Changjian Zhou , Yuexi Qiu , Jia Song

Inverse protein folding generates valid amino acid sequences that can fold into a desired protein structure, with recent deep-learning advances showing strong potential and competitive performance. However, challenges remain, such as…

Biomolecules · Quantitative Biology 2025-07-29 Peizhen Bai , Filip Miljković , Xianyuan Liu , Leonardo De Maria , Rebecca Croasdale-Wood , Owen Rackham , Haiping Lu

Understanding how proteins structurally interact is crucial to modern biology, with applications in drug discovery and protein design. Recent machine learning methods have formulated protein-small molecule docking as a generative problem…

Despite recent advancements in deep learning methods for protein structure prediction and representation, little focus has been directed at the simultaneous inclusion and prediction of protein backbone and sidechain structure information.…

Biomolecules · Quantitative Biology 2020-11-17 Jonathan E. King , David Ryan Koes

Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…

Quantitative Methods · Quantitative Biology 2024-11-04 Liang He , Peiran Jin , Yaosen Min , Shufang Xie , Lijun Wu , Tao Qin , Xiaozhuan Liang , Kaiyuan Gao , Yuliang Jiang , Tie-Yan Liu

Protein inverse folding, the design of an amino acid sequence based on a target protein structure, is a fundamental problem of computational protein engineering. Existing methods either generate sequences without leveraging external…

Quantitative Methods · Quantitative Biology 2026-03-10 Jin Han , Tianfan Fu , Wu-Jun Li

Coarse-grained (CG) models play a crucial role in the study of protein structures, protein thermodynamic properties, and protein conformation dynamics. Due to the information loss in the coarse-graining process, backmapping from CG to…

Quantitative Methods · Quantitative Biology 2023-11-30 Yikai Liu , Ming Chen , Guang Lin

Directed evolution plays an indispensable role in protein engineering that revises existing protein sequences to attain new or enhanced functions. Accurately predicting the effects of protein variants necessitates an in-depth understanding…

Quantitative Methods · Quantitative Biology 2023-06-09 Yang Tan , Bingxin Zhou , Yuanhong Jiang , Yu Guang Wang , Liang Hong

Proposing beneficial amino acid substitutions, whether for mutational effect prediction or protein engineering, remains a central challenge in structural biology. Recent inverse folding models, trained to reconstruct sequences from…

Biomolecules · Quantitative Biology 2025-12-12 Han Tang , Wouter Boomsma

Protein-protein interactions are central mediators in many biological processes. Accurately predicting the effects of mutations on interactions is crucial for guiding the modulation of these interactions, thereby playing a significant role…

Machine Learning · Computer Science 2024-05-29 Yuanle Mo , Xin Hong , Bowen Gao , Yinjun Jia , Yanyan Lan

In recent years, there has been a surge in the development of 3D structure-based pre-trained protein models, representing a significant advancement over pre-trained protein language models in various downstream tasks. However, most existing…

Machine Learning · Computer Science 2024-06-04 Jiale Zhao , Wanru Zhuang , Jia Song , Yaqi Li , Shuqi Lu

Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…

Biomolecules · Quantitative Biology 2017-01-18 Thomas A. Hopf , John B. Ingraham , Frank J. Poelwijk , Michael Springer , Chris Sander , Debora S. Marks

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction,…

Biomolecules · Quantitative Biology 2022-11-28 Kevin E. Wu , Kevin K. Yang , Rianne van den Berg , James Y. Zou , Alex X. Lu , Ava P. Amini
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