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Computational docking methods can provide structural models of protein-protein complexes, but protein backbone flexibility upon association often thwarts accurate predictions. In recent blind challenges, medium or high accuracy models were…

Biomolecules · Quantitative Biology 2020-12-29 Ameya Harmalkar , Jeffrey J. Gray

Predicting the structure of multi-protein complexes is a grand challenge in biochemistry, with major implications for basic science and drug discovery. Computational structure prediction methods generally leverage pre-defined structural…

Biomolecules · Quantitative Biology 2021-01-26 Stephan Eismann , Raphael J. L. Townshend , Nathaniel Thomas , Milind Jagota , Bowen Jing , Ron O. Dror

The method of Probability Density Profile Analysis has been introduced previously as a tool to find the best match between a set of experimentally generated Residual Dipolar Couplings and a set of known protein structures. While it proved…

Biomolecules · Quantitative Biology 2019-11-07 Ryan Yandle , Rishi Mukhopadhyay , Homayoun Valafar

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Statistical Mechanics · Physics 2026-05-08 Michael A. Sauer , Souvik Mondal , Brandon Neff , Sthitadhi Maiti , Matthias Heyden

Interacting proteins coevolve at multiple but interconnected scales, from the residue-residue over the protein-protein up to the family-family level. The recent accumulation of enormous amounts of sequence data allows for the development of…

Biomolecules · Quantitative Biology 2019-06-25 Hendrik Szurmant , Martin Weigt

Predicting the effect of mutations in proteins is one of the most critical challenges in protein engineering; by knowing the effect a substitution of one (or several) residues in the protein's sequence has on its overall properties, could…

Computational Engineering, Finance, and Science · Computer Science 2020-10-08 David Medina-Ortiz , Sebastian Contreras , Juan Amado-Hinojosa , Jorge Torres-Almonacid , Juan A. Asenjo , Marcelo Navarrete , Álvaro Olivera-Nappa

Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the consequences of structural conservation on protein evolution. We study seven of the most studied protein folds,…

Soft Condensed Matter · Physics 2007-05-23 Ugo Bastolla , Markus Porto , H. Eduardo Roman , Michele Vendruscolo

Composed of amino acid chains that influence how they fold and thus dictating their function and features, proteins are a class of macromolecules that play a central role in major biological processes and are required for the structure,…

Quantitative Methods · Quantitative Biology 2022-07-15 Aaron Wang

A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

Accurate identification of protein nucleic-acid-binding residues poses a significant challenge with important implications for various biological processes and drug design. Many typical computational methods for protein analysis rely on a…

Biomolecules · Quantitative Biology 2023-12-21 Linglin Jing , Sheng Xu , Yifan Wang , Yuzhe Zhou , Tao Shen , Zhigang Ji , Hui Fang , Zhen Li , Siqi Sun

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

Retrieving homologous protein sequences is essential for a broad range of protein modeling tasks such as fitness prediction, protein design, structure modeling, and protein-protein interactions. Traditional workflows have relied on a…

Quantitative Methods · Quantitative Biology 2025-06-11 Ruben Weitzman , Peter Mørch Groth , Lood Van Niekerk , Aoi Otani , Yarin Gal , Debora Marks , Pascal Notin

Advances in deep learning have opened an era of abundant and accurate predicted protein structures; however, similar progress in protein ensembles has remained elusive. This review highlights several recent research directions towards…

Biomolecules · Quantitative Biology 2025-09-23 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

Numerous cellular functions rely on protein$\unicode{x2013}$protein interactions. Efforts to comprehensively characterize them remain challenged however by the diversity of molecular recognition mechanisms employed within the proteome. Deep…

Biomolecules · Quantitative Biology 2023-12-08 Julia R. Rogers , Gergő Nikolényi , Mohammed AlQuraishi

Inverse statistical approaches to determine protein structure and function from Multiple Sequence Alignments (MSA) are emerging as powerful tools in computational biology. However the underlying assumptions of the relationship between the…

Biomolecules · Quantitative Biology 2016-11-17 Hugo Jacquin , Amy Gilson , Eugene Shakhnovich , Simona Cocco , Rémi Monasson

Evolution in its course found a variety of solutions to the same optimisation problem. The advent of high-throughput genomic sequencing has made available extensive data from which, in principle, one can infer the underlying structure on…

Quantitative Methods · Quantitative Biology 2016-04-12 Silvia Grigolon , Silvio Franz , Matteo Marsili

Amino acid sequence portrays most intrinsic form of a protein and expresses primary structure of protein. The order of amino acids in a sequence enables a protein to acquire a particular stable conformation that is responsible for the…

Machine Learning · Computer Science 2022-08-29 Ashish Ranjan , Md Shah Fahad , David Fernandez-Baca , Akshay Deepak , Sudhakar Tripathi

Recent generative learning models applied to protein multiple sequence alignment (MSA) datasets include simple and interpretable physics-based Potts covariation models and other machine learning models such as MSA-Transformer (MSA-T). The…

Biological Physics · Physics 2025-10-28 Kisan Khatri , Ronald M. Levy , Allan Haldane

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated…

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