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How do protein structure prediction models fold proteins? We investigate this question by tracing how ESMFold folds a beta hairpin, a prevalent structural motif. Through counterfactual interventions on model latents, we identify two…

Machine Learning · Computer Science 2026-02-10 Kevin Lu , Jannik Brinkmann , Stefan Huber , Aaron Mueller , Yonatan Belinkov , David Bau , Chris Wendler

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

This paper presents a method of reconstruction a primary structure of a protein that folds into a given geometrical shape. This method predicts the primary structure of a protein and restores its linear sequence of amino acids in the…

Quantitative Methods · Quantitative Biology 2017-01-04 Andrii Riazanov , Mikhail Karasikov , Sergei Grudinin

A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…

Biomolecules · Quantitative Biology 2018-08-09 William M. Jacobs , Eugene I. Shakhnovich

Predicting changes in binding free energy ($\Delta\Delta G$) is a vital task in protein engineering and protein-protein interaction (PPI) engineering for drug discovery. Previous works have observed a high correlation between $\Delta\Delta…

Machine Learning · Computer Science 2025-08-15 Patrick Soga , Zhenyu Lei , Yinhan He , Camille Bilodeau , Jundong Li

Protein structure prediction can be shown to be an NP-hard problem; the number of conformations grows exponentially with the number of residues. The native conformations of proteins occupy a very small subset of these, hence an exploratory,…

Chemical Physics · Physics 2008-02-03 Mehul M. Khimasia , Peter V. Coveney

Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the…

Populations and Evolution · Quantitative Biology 2007-05-23 Jesse D Bloom , Alpan Raval , Claus O Wilke

Native contacts between residues could be predicted from the amino acid sequence of proteins, and the predicted contact information could assist the de novo protein structure prediction. Here, we present a novel pipeline of a residue…

Biomolecules · Quantitative Biology 2019-05-29 Wenzhi Mao , Wenze Ding , Haipeng Gong

Many applications of machine learning methods involve an iterative protocol in which data are collected, a model is trained, and then outputs of that model are used to choose what data to consider next. For example, one data-driven approach…

Machine Learning · Computer Science 2025-04-07 Clara Fannjiang , Stephen Bates , Anastasios N. Angelopoulos , Jennifer Listgarten , Michael I. Jordan

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…

The classical approach to protein folding inspired by statistical mechanics avoids the high dimensional structure of the conformation space by using effective coordinates. Here we introduce a network approach to capture the statistical…

Biomolecules · Quantitative Biology 2007-05-23 Erzsebet Ravasz , S. Gnanakaran , Zoltan Toroczkai

The biological properties of proteins are uniquely determined by their structure and dynamics. A protein in solution populates a structural ensemble of metastable configurations around the global fold. From overall rotation to local…

Biological Physics · Physics 2015-12-09 J. Copperman , M. G. Guenza

Understanding how protein mutations affect protein structure is essential for advancements in computational biology and bioinformatics. We introduce PRIMRose, a novel approach that predicts energy values for each residue given a mutated…

Biomolecules · Quantitative Biology 2025-12-09 Stella Brown , Nicolas Preisig , Autumn Davis , Brian Hutchinson , Filip Jagodzinski

AlphaFold 3 (AF3) is a powerful biomolecular structure-predicting tool based on the latest deep learning algorithms and revolutionized AI model architectures. A few of papers have already investigated its accuracy in predicting different…

Biomolecules · Quantitative Biology 2025-11-19 Yiyang Xu , Ziyou Shen , Yanqing Lv , Shutong Tan , Chun Sun , Juan Zhang

Predicting which proteins interact together from amino-acid sequences is an important task. We develop a method to pair interacting protein sequences which leverages the power of protein language models trained on multiple sequence…

Biomolecules · Quantitative Biology 2024-12-30 Umberto Lupo , Damiano Sgarbossa , Anne-Florence Bitbol

Accurate prediction of protein-protein binding affinity is vital for understanding molecular interactions and designing therapeutics. We adapt Boltz-2, a state-of-the-art structure-based protein-ligand affinity predictor, for…

Machine Learning · Computer Science 2025-12-09 James King , Lewis Cornwall , Andrei Cristian Nica , James Day , Aaron Sim , Neil Dalchau , Lilly Wollman , Joshua Meyers

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

Motivation: Proteins are known to undergo conformational changes in the course of their functions. The changes in conformation are often attributable to a small fraction of residues within the protein. Therefore identification of these…

Biomolecules · Quantitative Biology 2011-10-31 Naoto Morikawa

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar…

Populations and Evolution · Quantitative Biology 2009-04-16 Jesse D. Bloom , Zhongyi Lu , David Chen , Alpan Raval , Ophelia S. Venturelli , Frances H. Arnold

Collecting genomics data across multiple heterogeneous populations (e.g., across different cancer types) has the potential to improve our understanding of disease. Despite sequencing advances, though, resources often remain a constraint…

Methodology · Statistics 2024-03-05 Yunyi Shen , Lorenzo Masoero , Joshua G. Schraiber , Tamara Broderick