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The accurate prediction of antigen-antibody structures is essential for advancing immunology and therapeutic development, as it helps elucidate molecular interactions that underlie immune responses. Despite recent progress with deep…

Biomolecules · Quantitative Biology 2024-12-16 Jie Gao , Jing Hu , Lihang Liu , Yang Xue , Kunrui Zhu , Xiaonan Zhang , Xiaomin Fang

The AlphaFold series has transformed protein structure prediction with remarkable accuracy, often matching experimental methods. AlphaFold2, AlphaFold-Multimer, and the latest AlphaFold3 represent significant strides in predicting single…

AI-based protein structure prediction pipelines, such as AlphaFold2, have achieved near-experimental accuracy. These advanced pipelines mainly rely on Multiple Sequence Alignments (MSAs) as inputs to learn the co-evolution information from…

Biomolecules · Quantitative Biology 2023-10-19 Xiaomin Fang , Fan Wang , Lihang Liu , Jingzhou He , Dayong Lin , Yingfei Xiang , Xiaonan Zhang , Hua Wu , Hui Li , Le Song

Predicting the structure of interacting chains is crucial for understanding biological systems and developing new drugs. Large-scale pre-trained Protein Language Models (PLMs), such as ESM2, have shown impressive abilities in extracting…

Biomolecules · Quantitative Biology 2023-12-05 Shuxian Zou , Hui Li , Shentong Mo , Xingyi Cheng , Eric Xing , Le Song

Antibody engineering is essential for developing therapeutics and advancing biomedical research. Traditional discovery methods often rely on time-consuming and resource-intensive experimental screening. To enhance and streamline this…

Biomolecules · Quantitative Biology 2025-07-04 Jie Gao , Jing Hu , Shanzhuo Zhang , Kunrui Zhu , Sheng Qian , Yueyang Huang , Xiaonan Zhang , Xiaomin Fang

Accurate protein structure prediction can significantly accelerate the development of life science. The accuracy of AlphaFold2, a frontier end-to-end structure prediction system, is already close to that of the experimental determination…

Distributed, Parallel, and Cluster Computing · Computer Science 2022-07-14 Guoxia Wang , Xiaomin Fang , Zhihua Wu , Yiqun Liu , Yang Xue , Yingfei Xiang , Dianhai Yu , Fan Wang , Yanjun Ma

AlphaFold has transformed protein structure prediction, but emerging applications such as virtual ligand screening, proteome-wide folding, and de novo binder design demand predictions at a massive scale, where runtime and memory costs…

AlphaFold 3 (AF3), the latest version of protein structure prediction software, goes beyond its predecessors by predicting protein-protein complexes. It could revolutionize drug discovery and protein engineering, marking a major step…

Biomolecules · Quantitative Biology 2024-06-07 JunJie Wee , Guo-Wei Wei

The binding complexes formed by proteins and small molecule ligands are ubiquitous and critical to life. Despite recent advancements in protein structure prediction, existing algorithms are so far unable to systematically predict the…

Quantitative Methods · Quantitative Biology 2023-04-21 Zhuoran Qiao , Weili Nie , Arash Vahdat , Thomas F. Miller , Anima Anandkumar

Proteins are fundamental components of biological systems and can be represented through various modalities, including sequences, structures, and textual descriptions. Despite the advances in deep learning and scientific large language…

Machine Learning · Computer Science 2024-07-15 Zhiyuan Chen , Tianhao Chen , Chenggang Xie , Yang Xue , Xiaonan Zhang , Jingbo Zhou , Xiaomin Fang

Understanding the 3D structures of protein multimers is crucial, as they play a vital role in regulating various cellular processes. It has been empirically confirmed that the multimer structure prediction~(MSP) can be well handled in a…

Computational Engineering, Finance, and Science · Computer Science 2024-03-01 Ziqi Gao , Xiangguo Sun , Zijing Liu , Yu Li , Hong Cheng , Jia Li

Determining the structure of a protein has been a decades-long open question. A protein's three-dimensional structure often poses nontrivial computation costs, when classical simulation algorithms are utilized. Advances in the transformer…

Machine Learning · Computer Science 2023-10-09 Chen Dun , Qiutai Pan , Shikai Jin , Ria Stevens , Mitchell D. Miller , George N. Phillips, , Anastasios Kyrillidis

Recent advancements in protein structure prediction, particularly AlphaFold2, have revolutionized structural biology by achieving near-experimental accuracy ($\text{average RMSD} < 1.5\text{\AA}$). However, the computational demands of…

Biomolecules · Quantitative Biology 2025-06-09 Joongwon Chae , Zhenyu Wang , Ijaz Gul , Jiansong Ji , Zhenglin Chen , Peiwu Qin

Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…

Biomolecules · Quantitative Biology 2025-06-18 Advaith Maddipatla , Nadav Bojan Sellam , Meital Bojan , Sanketh Vedula , Paul Schanda , Ailie Marx , Alex M. Bronstein

Protein binder design is central to therapeutics, diagnostics, and synthetic biology, yet practical deployment remains challenging due to fragmented workflows, high computational costs, and complex tool integration. We present…

Biomolecules · Quantitative Biology 2025-05-29 Jie Gao , Jun Li , Jing Hu , Shanzhuo Zhang , Kunrui Zhu , Yueyang Huang , Xiaonan Zhang , Xiaomin Fang

Even with the significant advances of AlphaFold-Multimer (AF-Multimer) and AlphaFold3 (AF3) in protein complex structure prediction, their accuracy is still not comparable with monomer structure prediction. Efficient quality assessment (QA)…

Biomolecules · Quantitative Biology 2024-10-24 Bingqing Han , Yipeng Zhang , Longlong Li , Xinqi Gong , Kelin Xia

The design and optimization of antibodies requires an intricate balance across multiple properties. Protein inverse folding models, capable of generating diverse sequences folding into the same structure, are promising tools for maintaining…

Protein structure generative models excel at predicting single protein static structures from sequence, but routinely fail to capture the correct conformational state of protein complexes, critical for protein design and induced proximity…

Machine Learning · Computer Science 2026-05-27 Alon Shtrikman , Nitzan Simchi , Michal Ran Shchory , Sagie Brodsky , Eran Seger , Kirill Pevzner

Protein-ligand structure prediction is an essential task in drug discovery, predicting the binding interactions between small molecules (ligands) and target proteins (receptors). Recent advances have incorporated deep learning techniques to…

Models such as AlphaFold2 and OpenFold have transformed protein structure prediction, yet their inner workings remain poorly understood. We present a methodology to systematically evaluate the contribution of individual OpenFold components…

Biomolecules · Quantitative Biology 2025-11-20 Tyler L. Hayes , Giri P. Krishnan
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