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The goal of Protein Structure Prediction (PSP) problem is to predict a protein's 3D structure (confirmation) from its amino acid sequence. The problem has been a 'holy grail' of science since the Noble prize-winning work of Anfinsen…

Biomolecules · Quantitative Biology 2023-01-24 Abbi Abdel-Rehim , Oghenejokpeme Orhobor , Hang Lou , Hao Ni , Ross D. King

AlphaFold2 has been hailed as a breakthrough in protein folding. It can rapidly predict protein structures with lab-grade accuracy. However, its implementation does not include the necessary training code. OpenFold is the first trainable…

The AlphaFold Protein Structure Database (AFDB) offers unparalleled structural coverage at near-experimental accuracy, positioning it as a valuable resource for data-driven protein design. However, its direct use in training deep models…

Machine Learning · Computer Science 2025-06-11 Cheng Tan , Zhenxiao Cao , Zhangyang Gao , Siyuan Li , Yufei Huang , Stan Z. Li

AlphaFold3 introduces a diffusion-based architecture that elevates protein structure prediction to all-atom resolution with improved accuracy. This state-of-the-art performance has established AlphaFold3 as a foundation model for diverse…

Machine Learning · Computer Science 2026-05-19 Zhe Zhang , Yuanning Feng , Yuxuan Song , Keyue Qiu , Hao Zhou , Wei-Ying Ma

AlphaFold2 (AF2) has transformed protein structure prediction by harnessing co-evolutionary constraints embedded in multiple sequence alignments (MSAs). MSAs not only encode static structural information, but also hold critical details…

Biomolecules · Quantitative Biology 2025-03-04 Enming Xing , Junjie Zhang , Shen Wang , Xiaolin Cheng

Recent advancements in machine learning (ML) are transforming the field of structural biology. For example, AlphaFold, a groundbreaking neural network for protein structure prediction, has been widely adopted by researchers. The…

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

Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…

Machine Learning · Computer Science 2025-02-27 Gregory W. Kyro , Tianyin Qiu , Victor S. Batista

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

Computationally predicting protein-protein interactions (PPIs) is challenging due to the lack of integrated, multimodal protein representations. DPEB is a curated collection of 22,043 human proteins that integrates four embedding types:…

Deep learning-based approaches, such as AlphaFold2 (AF2), have significantly advanced protein tertiary structure prediction, achieving results comparable to real biological experimental methods. While AF2 has shown limitations in predicting…

Biomolecules · Quantitative Biology 2025-01-23 Zhongju Yuan , Tao Shen , Sheng Xu , Leiye Yu , Ruobing Ren , Siqi Sun

The computer artificial intelligence system AlphaFold has recently predicted previously unknown three-dimensional structures of thousands of proteins. Focusing on the subset with high-confidence scores, we algorithmically analyze these…

Biomolecules · Quantitative Biology 2022-07-18 Maarten A. Brems , Robert Runkel , Todd O. Yeates , Peter Virnau

G-Protein Coupled Receptors (GPCRs) are integral to numerous physiological processes and are the target of approximately one-third of FDA-approved therapeutics. Despite their significance, only a limited subset of GPCRs has been…

Quantitative Methods · Quantitative Biology 2025-02-26 Garima Chib , Parisa Mollaei , Amir Barati Farimani

Proteins perform critical processes in all living systems: converting solar energy into chemical energy, replicating DNA, as the basis of highly performant materials, sensing and much more. While an incredible range of functionality has…

Biomolecules · Quantitative Biology 2021-09-29 Leonardo V. Castorina , Rokas Petrenas , Kartic Subr , Christopher W. Wood

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

In recent years, advances in artificial intelligence (AI) have transformed structural biology, particularly protein structure prediction. Though AI-based methods, such as AlphaFold (AF), often predict single conformations of proteins with…

Biomolecules · Quantitative Biology 2024-10-22 Devlina Chakravarty , Myeongsang Lee , Lauren L. Porter

In the field of antibody engineering, an essential task is to design a novel antibody whose paratopes bind to a specific antigen with correct epitopes. Understanding antibody structure and its paratope can facilitate a mechanistic…

Quantitative Methods · Quantitative Biology 2023-05-08 Yining Wang , Xumeng Gong , Shaochuan Li , Bing Yang , YiWu Sun , Chuan Shi , Yangang Wang , Cheng Yang , Hui Li , Le Song

We present TerraBind, a foundation model for protein-ligand structure and binding affinity prediction that achieves 26-fold faster inference than state-of-the-art methods while improving affinity prediction accuracy by $\sim$20\%. Current…

Small molecule drug design hinges on obtaining co-crystallized ligand-protein structures. Despite AlphaFold2's strides in protein native structure prediction, its focus on apo structures overlooks ligands and associated holo structures.…

Biological Physics · Physics 2024-07-08 Xinyu Gu , Akashnathan Aranganathan , Pratyush Tiwary

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai