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Due to the lack of a method to efficiently represent the multimodal information of a protein, including its structure and sequence information, predicting compound-protein binding affinity (CPA) still suffers from low accuracy when applying…

Biomolecules · Quantitative Biology 2022-11-28 Binjie Guo , Hanyu Zheng , Haohan Jiang , Xiaodan Li , Naiyu Guan , Yanming Zuo , Yicheng Zhang , Hengfu Yang , Xuhua Wang

Proteins are essential components of living systems, capable of performing a huge variety of tasks at the molecular level, such as recognition, signalling, copy, transport, ... The protein sequences realizing a given function may largely…

Biomolecules · Quantitative Biology 2016-02-17 John Barton , Arup Chakraborty , Simona Cocco , Hugo Jacquin , Rémi Monasson

What are the structural determinants of protein sequence evolution? A number of site-specific structural characteristics have been proposed, most of which are broadly related to either the density of contacts or the solvent accessibility of…

Biological Physics · Physics 2017-01-31 Amir Shahmoradi , Claus Wilke

A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven different helix bundle proteins. The protocol, which includes…

Biomolecules · Quantitative Biology 2009-11-11 Isaac A. Hubner , Eric J. Deeds , Eugene I. Shakhnovich

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…

Many models of interest in the natural and social sciences have no closed-form likelihood function, which means that they cannot be treated using the usual techniques of statistical inference. In the case where such models can be…

Computation · Statistics 2012-07-19 Simon Barthelmé , Nicolas Chopin

Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…

Biomolecules · Quantitative Biology 2017-03-16 Rocío Espada , R. Gonzalo Parra , Thierry Mora , Aleksandra M. Walczak , Diego U. Ferreiro

Generative artificial intelligence models learn probability distributions from data and produce novel samples that capture the salient properties of their training sets. Proteins are particularly attractive for such approaches given their…

Biomolecules · Quantitative Biology 2026-02-27 Filippo Stocco , Michele Garibbo , Noelia Ferruz

We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wildtype structure after one or more random amino acid substitutions. Our theory predicts that for large numbers of…

Biomolecules · Quantitative Biology 2009-11-10 Jesse D. Bloom , Jonathan J. Silberg , Claus O. Wilke , D. Allan Drummond , Christoph Adami , Frances H. Arnold

The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…

Biological Physics · Physics 2015-05-28 Walter Simmons , Joel L. Weiner

Predicting the binding affinity of protein protein complexes directly from sequence remains a challenging problem, particularly in the absence of reliable structural information. Here I present ProtT Affinity, a sequence only model that…

Quantitative Methods · Quantitative Biology 2025-11-21 Hongfu Lou

Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein,…

Biomolecules · Quantitative Biology 2019-04-26 Shou-Wen Wang , Anne-Florence Bitbol , Ned S. Wingreen

Protein interaction networks aim to summarize the complex interplay of proteins in an organism. Early studies suggested that the position of a protein in the network determines its evolutionary rate but there has been considerable…

Molecular Networks · Quantitative Biology 2007-05-23 Ino Agrafioti , Jonathan Swire , James Abbott , Derek Huntley , Sarah Butcher , Michael P. H. Stumpf

Accurately predicting protein structures from amino acid sequences remains a fundamental challenge in computational biology, with profound implications for understanding biological functions and enabling structure-based drug discovery.…

Nucleic acid-based drugs like aptamers have recently demonstrated great therapeutic potential. However, experimental platforms for aptamer screening are costly, and the scarcity of labeled data presents a challenge for supervised methods to…

Biomolecules · Quantitative Biology 2024-11-05 Tinglin Huang , Zhenqiao Song , Rex Ying , Wengong Jin

The accurate prediction of changes in protein stability under multiple amino acid substitutions is essential for realising true in-silico protein re-design. To this purpose, we propose improvements to state-of-the-art Deep learning (DL)…

Biomolecules · Quantitative Biology 2023-06-01 Sebastien Boyer , Sam Money-Kyrle , Oliver Bent

Predicting interactions between proteins is one of the most important yet challenging problems in structural bioinformatics. Intrinsically, potential function sites in protein surfaces are determined by both geometric and chemical features.…

Biomolecules · Quantitative Biology 2024-01-19 Yiqun Lin , Liang Pan , Yi Li , Ziwei Liu , Xiaomeng Li

Proteins and other macromolecules exist not in a single state but as dynamic ensembles of interconverting conformations, which are essential for catalysis, allosteric regulation, and molecular recognition. While AI-based structure…

Biomolecules · Quantitative Biology 2025-10-22 Stephanie A. Wankowicz , Massimiliano Bonomi

In multi-resolution simulations, different system components are simultaneously modelled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is…

Biological Physics · Physics 2016-11-03 Aoife C. Fogarty , Raffaello Potestio , Kurt Kremer

We present a statistical approach to protein structure by introducing a representation of protein folds based on simple observables defined as frequencies of oriented cycles in contact graphs. Motivated by the idea that these cycles may…

Biomolecules · Quantitative Biology 2016-09-08 A. M. Lisewski , O. Lichtarge