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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

Fluctuations in the abundance of molecules in the living cell may affect its growth and well being. For regulatory molecules (e.g., signaling proteins or transcription factors), fluctuations in their expression can affect the levels of…

Molecular Networks · Quantitative Biology 2009-11-13 Erel Levine , Terence Hwa

Learning Ising or Potts models from data has become an important topic in statistical physics and computational biology, with applications to predictions of structural contacts in proteins and other areas of biological data analysis. The…

Biological Physics · Physics 2018-09-19 Chen-Yi Gao , Hai-Jun Zhou , Erik Aurell

Standard methods for aligning large language models with human preferences learn from pairwise comparisons among sampled candidate responses and regularize toward a reference policy. Despite their effectiveness, the effects of sampling and…

Machine Learning · Computer Science 2026-02-13 Yurong Chen , Yu He , Michael I. Jordan , Fan Yao

Traditionally evolution is seen as a process where from a pool of possible variations of a population (e.g. biological species or industrial goods) a few variations get selected which survive and proliferate, whereas the others vanish.…

Populations and Evolution · Quantitative Biology 2008-09-25 Rudolf Hanel , Stefan Thurner

This paper considers the evolution of a network in a discrete time, stochastic setting in which agents learn about each other through repeated interactions and maintain/break links on the basis of what they learn from these interactions.…

Physics and Society · Physics 2015-11-27 Mihaela van der Schaar , Simpson Zhang

Knotted proteins embed a physical (i.e., open) knot within their native structures. For decades, significant effort has been devoted to elucidating the functional role of knots in proteins, yet no consensus has been reached. Here, using…

Biomolecules · Quantitative Biology 2026-03-13 João NC Especial , Patrícia FN Faísca

Deep neural networks such as AlphaFold and RoseTTAFold predict remarkably accurate structures of proteins compared to other algorithmic approaches. It is known that biologically small perturbations in the protein sequence do not lead to…

Biomolecules · Quantitative Biology 2021-09-21 Sumit Kumar Jha , Arvind Ramanathan , Rickard Ewetz , Alvaro Velasquez , Susmit Jha

Summary statistics of the likelihood, such as the Bayesian evidence, offer a principled way of comparing models and assessing tension between, or within, the results of physical experiments. Noisy realisations of the data induce scatter in…

Cosmology and Nongalactic Astrophysics · Physics 2021-04-30 B. Joachimi , F. Köhlinger , W. Handley , P. Lemos

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

In evolutionary algorithms, the fitness of a population increases with time by mutating and recombining individuals and by a biased selection of more fit individuals. The right selection pressure is critical in ensuring sufficient…

Artificial Intelligence · Computer Science 2007-05-23 Marcus Hutter

Directed evolution is an iterative laboratory process of designing proteins with improved function by iteratively synthesizing new protein variants and evaluating their desired property with expensive and time-consuming biochemical…

Machine Learning · Computer Science 2025-09-08 Matouš Soldát , Jiří Kléma

Knots are abundant in globular homopolymers but rare in globular proteins. To shed new light on this long-standing conundrum, we study the influence of sequence on the formation of knots in proteins under native conditions within the…

Soft Condensed Matter · Physics 2015-03-17 Thomas Wüst , Daniel Reith , Peter Virnau

Biological processes, functions, and properties are intricately linked to the ensemble of protein conformations, rather than being solely determined by a single stable conformation. In this study, we have developed P2DFlow, a generative…

Biological Physics · Physics 2025-03-05 Yaowei Jin , Qi Huang , Ziyang Song , Mingyue Zheng , Dan Teng , Qian Shi

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

Motivation: Protein interactions are fundamental building blocks of biochemical reaction systems underlying cellular functions. The complexity and functionality of such systems emerge not from the protein interactions themselves but from…

Molecular Networks · Quantitative Biology 2011-06-15 Johannes Köster , Eli Zamir , Sven Rahmann

Genome length varies widely among organisms, from compact genomes of prokaryotes to vast and complex genomes of eukaryotes. In this study, we theoretically identify the evolutionary pressures that may have driven this divergence in genome…

Genomics · Quantitative Biology 2025-03-03 Parthasarathi Sahu , Sashikanta Barik , Koushik Ghosh , Hemachander Subramanian

Gene products (RNAs, proteins) often occur at low molecular counts inside individual cells, and hence are subject to considerable random fluctuations (noise) in copy number over time. Not surprisingly, cells encode diverse regulatory…

Molecular Networks · Quantitative Biology 2015-10-01 Thierry Platini , Mohammad Soltani , Abhyudai Singh

Characterization of protein energy landscape and conformational ensembles is important for understanding mechanisms of protein folding and function. We studied ensembles of bound and unbound conformations of six proteins to explore their…

Biological Physics · Physics 2012-11-06 Anatoly M. Ruvinsky , Tatsiana Kirys , Alexander V. Tuzikov , Ilya A. Vakser

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