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Predicting protein properties is paramount for biological and medical advancements. Current protein engineering mutates on a typical protein, called the wild-type, to construct a family of homologous proteins and study their properties.…

Machine Learning · Computer Science 2024-06-26 Zhiqiang Zhong , Davide Mottin

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of…

Populations and Evolution · Quantitative Biology 2011-07-26 E. Alejandro Herrada , Víctor M. Eguíluz , Emilio Hernández-García , Carlos M. Duarte

What are the molecular mechanisms that dictate protein-protein binding stability and whether those are related to the ones behind protein fold stability are still largely open questions. Indeed, despite many past efforts, we still lack…

Biological Physics · Physics 2023-11-28 Fausta Desantis , Mattia Miotto , Lorenzo Di Rienzo , Edoardo Milanetti , Giancarlo Ruocco

Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…

Biological Physics · Physics 2019-11-25 Frank Noé , Gianni De Fabritiis , Cecilia Clementi

In this work we propose a physical model of organismal evolution, where phenotype, organism life expectancy, is directly related to genotype i.e. the stability of its proteins which can be determined exactly in the model. Simulating the…

Populations and Evolution · Quantitative Biology 2007-05-23 Konstantin B. Zeldovich , Boris E. Shakhnovich , Eugene I. Shakhnovich

We study folding in 16-monomer heteropolymers on the square lattice. For a given sequence, thermodynamic properties and stability of the native state are unique. However, the kinetics of folding depends on the model of dynamics adopted for…

Statistical Mechanics · Physics 2009-10-31 Trinh Xuan Hoang , Marek Cieplak

The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…

Populations and Evolution · Quantitative Biology 2015-06-11 Premal Shah , David M. McCandlish , Joshua B. Plotkin

We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in…

Condensed Matter · Physics 2009-11-07 Ugo Bastolla , Markus Porto , H. Eduardo Roman , Michele Vendruscolo

Understanding the observed variability in the number of homologs of a gene is a very important, unsolved problem that has broad implications for research into co-evolution of structure and function, gene duplication, pseudogene formation…

Biomolecules · Quantitative Biology 2007-05-23 Boris Shakhnovich , Eric Deeds , Charles Delisi , Eugene Shakhnovich

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

Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins.…

Biomolecules · Quantitative Biology 2014-04-01 Ernesto A. Roman , F. Luis Gonzalez Flecha

We solve a model that takes into account entropic barriers, frustration, and the organization of a protein-like molecule. For a chain of size $M$, there is an effective folding transition to an ordered structure. Without frustration, this…

Condensed Matter · Physics 2009-10-28 Carlos J. Camacho

Protein binding and function often involves conformational changes. Advanced NMR experiments indicate that these conformational changes can occur in the absence of ligand molecules (or with bound ligands), and that the ligands may 'select'…

Biomolecules · Quantitative Biology 2014-09-10 Thomas R. Weikl , Fabian Paul

Proteins are linear molecular chains that often fold to function. The topology of folding is widely believed to define its properties and function, and knot theory has been applied to study protein structure and its implications. More that…

Geometric Topology · Mathematics 2020-07-13 Colin Adams , Judah Devadoss , Mohamed Elhamdadi , Alireza Mashaghi

Hybridization between species is an important mechanism for the origin of novel lineages and adaptation to new environments. Increased allelic variation and modification of the transcriptional network are the two recognized forces currently…

Genomics · Quantitative Biology 2013-10-24 Elzbieta M. Piatkowska , David Knight , Daniela Delneri

Cooperativity is a hallmark of proteins, many of which show a modular architecture comprising discrete structural domains. Detecting and describing dynamic couplings between structural regions is difficult in view of the many-body nature of…

Biological Physics · Physics 2015-02-03 Olga Kononova , Lee Jones , Valeri Barsegov

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

Cooperativity plays an important role in the action of proteins bound to DNA. A simple, mechanical mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations is…

Soft Condensed Matter · Physics 2009-10-31 Joseph Rudnick , Robijn Bruinsma

Protein folding cooperativity is defined by the nature of the finite-size thermodynamic transition exhibited upon folding: two-state transitions show a free energy barrier between the folded and unfolded ensembles, while downhill folding is…

Biomolecules · Quantitative Biology 2017-08-23 Tristan Bereau , Michael Bachmann , Markus Deserno

Protein folding and evolution are intimately linked phenomena. Here, we revisit the concept of exons as potential protein folding modules across 38 abundant and conserved protein families. Taking advantage of genomic exon-intron…

Biomolecules · Quantitative Biology 2024-01-05 Ezequiel A. Galpern , Hana Jaafari , Carlos Bueno , Peter G. Wolynes , Diego U. Ferreiro