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In Dec 2020, the results of AlphaFold2 were presented at CASP14, sparking a revolution in the field of protein structure predictions. For the first time, a purely computational method could challenge experimental accuracy for structure…

Biomolecules · Quantitative Biology 2022-12-16 Arne Elofsson

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

AlphaFold 3 represents a transformative advancement in computational biology, enhancing protein structure prediction through novel multi-scale transformer architectures, biologically informed cross-attention mechanisms, and geometry-aware…

Biomolecules · Quantitative Biology 2025-08-27 Alireza Abbaszadeh , Armita Shahlaee

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

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

The remarkable success of AlphaFold2 in providing accurate atomic-level prediction of protein structures from their amino acid sequence has transformed approaches to the protein folding problem. However, its core paradigm of mapping one…

Applications · Statistics 2025-12-12 Yongkai Chen , Samuel WK Wong , SC Kou

AlphaFold predicts protein structures from the amino acid sequence at or near experimental resolution, solving the 50-year-old protein folding challenge, leading to progress by transforming large-scale genomics data into protein structures.…

Biomolecules · Quantitative Biology 2021-11-16 Bozitao Zhong , Xiaoming Su , Minhua Wen , Sichen Zuo , Liang Hong , James Lin

This paper presents a novel approach for predicting the relative populations of protein conformations using AlphaFold 2, an AI-powered method that has revolutionized biology by enabling the accurate prediction of protein structures. While…

AlphaFold can be used for both single-chain and multi-chain protein structure prediction, while the latter becomes extremely challenging as the number of chains increases. In this work, by taking each chain as a node and assembly actions as…

Computational Engineering, Finance, and Science · Computer Science 2024-05-08 Ziqi Gao , Tao Feng , Jiaxuan You , Chenyi Zi , Yan Zhou , Chen Zhang , Jia Li

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

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…

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

The seminal breakthrough of AlphaFold in protein structure prediction relied on a learned potential energy function parameterized by deep models, in contrast to its successors AlphaFold2 and AlphaFold3, which lack an explicit probabilistic…

Machine Learning · Computer Science 2026-04-28 Thomas Hamelryck , Kanti V. Mardia

Motivation: Protein folding is a dynamic process during which a protein's amino acid sequence undergoes a series of 3-dimensional (3D) conformational changes en route to reaching a native 3D structure; the resulting 3D structural…

Biomolecules · Quantitative Biology 2026-04-09 Aydin Wells , Khalique Newaz , Jennifer Morones , Jianlin Cheng , Tijana Milenković

Protein structure prediction models such as AlphaFold3 (AF3) push the frontier of biomolecular modeling by incorporating science-informed architectural changes to the transformer architecture. However, these advances come at a steep system…

Biomolecules · Quantitative Biology 2025-06-27 Hoa La , Ahan Gupta , Alex Morehead , Jianlin Cheng , Minjia Zhang

Highly accurate biomolecular structure prediction is a key component of developing biomolecular foundation models, and one of the most critical aspects of building foundation models is identifying the recipes for scaling the model. In this…

Biomolecules · Quantitative Biology 2026-01-02 Yi Zhou , Chan Lu , Yiming Ma , Wei Qu , Fei Ye , Kexin Zhang , Lan Wang , Minrui Gui , Quanquan Gu

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

The prediction of protein 3D structure from amino acid sequence is a computational grand challenge in biophysics, and plays a key role in robust protein structure prediction algorithms, from drug discovery to genome interpretation. The…

Biomolecules · Quantitative Biology 2024-07-03 Hyun Park , Parth Patel , Roland Haas , E. A. Huerta

While DeepMind has tentatively solved protein folding, its inverse problem -- protein design which predicts protein sequences from their 3D structures -- still faces significant challenges. Particularly, the lack of large-scale standardized…

Quantitative Methods · Quantitative Biology 2022-02-15 Zhangyang Gao , Cheng Tan , Stan Z. Li

Designing an appropriate set of collective variables is crucial to the success of several enhanced sampling methods. Here we focus on how to obtain such variables from information limited to the metastable states. We characterize these…

Chemical Physics · Physics 2020-04-08 Luigi Bonati , Valerio Rizzi , Michele Parrinello
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