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Protein evolution involves mutations occurring across a wide range of time scales. In analogy with disordered systems in statistical physics, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct…

Biomolecules · Quantitative Biology 2025-07-15 Saverio Rossi , Leonardo Di Bari , Martin Weigt , Francesco Zamponi

The enormous size and complexity of genotypic sequence space frequently requires consideration of coarse-grained sequences in empirical models. We develop scaling relations to quantify the effect of this coarse-graining on properties of…

Populations and Evolution · Quantitative Biology 2015-06-01 Michael Manhart , Alexandre V. Morozov

Much scientific enquiry across disciplines is founded upon a mechanistic treatment of dynamic systems that ties form to function. A highly visible instance of this is in molecular biology, where an important goal is to determine…

Biomolecules · Quantitative Biology 2021-06-17 Xiaojie Guo , Yuanqi Du , Sivani Tadepalli , Liang Zhao , Amarda Shehu

We discuss a stochastic approach for reconstructing the native structures of proteins from the knowledge of the "effective connectivity", which is a one-dimensional structural profile constructed as a linear combination of the eigenvectors…

Biological Physics · Physics 2009-01-20 Katrin Wolff , Michele Vendruscolo , Markus Porto

Much information is stored in amino acid composition of protein and base composition of DNA. We simulated the evolution of amino acid frequencies and genomic GC content by a linguistic model. It is showed that the evolution of genetic code…

Genomics · Quantitative Biology 2007-05-23 Dirson Jian Li

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

Designing protein sequences with specific biological functions and structural stability is crucial in biology and chemistry. Generative models already demonstrated their capabilities for reliable protein design. However, previous models are…

Machine Learning · Computer Science 2024-02-28 Lin Zongying , Li Hao , Lv Liuzhenghao , Lin Bin , Zhang Junwu , Chen Calvin Yu-Chian , Yuan Li , Tian Yonghong

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

We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We…

Statistical Mechanics · Physics 2009-10-31 Ugo Bastolla , Michele Vendruscolo , H. Eduardo Roman

Protein structure prediction is one of the most important problems in computational biology. The most successful computational approach, also called template-based modeling, identifies templates with solved crystal structures for the query…

Biomolecules · Quantitative Biology 2013-06-20 Jian Peng

Recently, many generative models for de novo protein structure design have emerged. Yet, only few tackle the difficult task of directly generating fully atomistic structures jointly with the underlying amino acid sequence. This is…

The protein folding problem has attracted an increasing attention from physicists. The problem has a flavor of statistical mechanics, but possesses the most common feature of most biological problems -- the profound effects of evolution. I…

Statistical Mechanics · Physics 2009-10-31 Chao Tang

Mapping between sequence and structure is currently an open problem in structural biology. Despite many experimental and computational efforts it is not clear yet how the structure is encoded in the sequence. Answering this question may…

Biomolecules · Quantitative Biology 2013-10-08 Iddo Friedberg

Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…

Machine Learning · Computer Science 2025-10-01 Yogesh Verma , Markus Heinonen , Vikas Garg

The recent interest in human dynamics has led researchers to investigate the stochastic processes that explain human behaviour in different contexts. Here we propose a generative model to capture the essential dynamics of survival analysis,…

Physics and Society · Physics 2015-06-18 Trevor Fenner , Mark Levene , George Loizou

The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic…

Genomics · Quantitative Biology 2008-03-25 Jacob Bock Axelsen , Koon-Kiu Yan , Sergei Maslov

In the protein sequence space, natural proteins form clusters of families which are characterized by their unique native folds whereas the great majority of random polypeptides are neither clustered nor foldable to unique structures. Since…

Biomolecules · Quantitative Biology 2018-02-06 Akira R. Kinjo

Determining the different conformational states of a protein and the transition paths between them is key to fully understanding the relationship between biomolecular structure and function. This can be accomplished by sampling protein…

Biological Physics · Physics 2021-03-24 Venkata K. Ramaswamy , Chris G. Willcocks , Matteo T. Degiacomi

Proteins are the fundamental macromolecules that play diverse and crucial roles in all living matter and have tremendous implications in healthcare, manufacturing, and biotechnology. Their functions are largely determined by the sequences…

Biomolecules · Quantitative Biology 2024-09-17 Boqiao Lai

Binding interactions between proteins and other molecules mediate numerous cellular processes, including metabolism, signaling, and regulation of gene expression. These interactions evolve in response to changes in the protein's chemical or…

Populations and Evolution · Quantitative Biology 2015-02-19 Michael Manhart , Alexandre V. Morozov