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The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…

Biomolecules · Quantitative Biology 2024-11-15 Pranav Kantroo , Günter P. Wagner , Benjamin B. Machta

Proteins evolve through complex sequence spaces, with fitness landscapes serving as a conceptual framework that links sequence to function. Fitness landscapes can be smooth, where multiple similarly accessible evolutionary paths are…

Populations and Evolution · Quantitative Biology 2024-11-21 Mahakaran Sandhu , John Chen , Dana Matthews , Matthew A Spence , Sacha B Pulsford , Barnabas Gall , James Nichols , Nobuhiko Tokuriki , Colin J Jackson

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

We study folding dynamics of protein-like sequences on square lattice using physical move set that exhausts all possible conformational changes. By analytically solving the master equation, we follow the time-dependent probabilities of…

Biomolecules · Quantitative Biology 2016-08-16 Sëma Kachalo , Hsiao-Mei Lu , Jie Liang

Several recent works have shown that protein structure can predict site-specific evolutionary sequence variation. In particular, sites that are buried and/or have many contacts with other sites in a structure have been shown to evolve more…

In this study, the distributions of protein structure classes (or folding types) of experimentally determined structures from a legacy dataset and a comprehensive database (SCOP) are modeled precisely with geometric constructs such as…

Biomolecules · Quantitative Biology 2025-10-21 Boryeu Mao

Proteins are intricate molecular machines whose complexity arises from the heterogeneity of the amino acid building blocks and their dynamic network of many-body interactions. These nanomachines gain function when put in the context of a…

Biomolecules · Quantitative Biology 2023-12-14 John M. McBride , Tsvi Tlusty

Much evolutionary information is stored in the fluctuations of protein length distributions. The genome size and non-coding DNA content can be calculated based only on the protein length distributions. So there is intrinsic relationship…

Genomics · Quantitative Biology 2008-06-03 Dirson Jian Li , Shengli Zhang

How proteins fold remains a central unsolved problem in biology. While the idea of a folding code embedded in the amino acid sequence was introduced more than 6 decades ago, this code remains undefined. While we now have powerful predictive…

Biomolecules · Quantitative Biology 2025-11-04 Carlos Bustamante , Christian Kaiser , Erik Lindahl , Robert Sosa , Giovanni Volpe

Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we…

Populations and Evolution · Quantitative Biology 2007-05-23 D. Allan Drummond , Jesse D. Bloom , Christoph Adami , Claus O. Wilke , Frances H. Arnold

Atomic packing is an important metric for characterizing protein structures, as it significantly influences various features including the stability, the rate of evolution and the functional roles of proteins. Packing in protein structures…

Biomolecules · Quantitative Biology 2025-05-27 Sotirios Touliopoulos , Nicholas M. Glykos

The intricate three-dimensional geometries of protein tertiary structures underlie protein function and emerge through a folding process from one-dimensional chains of amino acids. The exact spatial sequence and configuration of amino…

Biomolecules · Quantitative Biology 2021-02-24 Nora Molkenthin , Steffen Mühle , Antonia S J S Mey , Marc Timme

A fast and accurate grid-based method with low memory requirement is presented to calculate volume characteristics in molecular systems. The distribution of volume and packing density is characterized in globular proteins, where void space…

Biological Physics · Physics 2018-10-23 Jenny Farmer , Sheridan B. Green , Donald J. Jacobs

Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances both in theory and experiments have resulted in a conceptual framework for describing…

Soft Condensed Matter · Physics 2010-07-20 D. Thirumalai , Edward P. O'Brien , Greg Morrison , Changbong Hyeon

Proteins are sequences of amino acids that serve as the basic building blocks of living organisms. Despite rapidly growing databases documenting structural and functional information for various protein sequences, our understanding of…

Biomolecules · Quantitative Biology 2025-01-06 Weihang Dai

The concept of robustness of regulatory networks has been closely related to the nature of the interactions among genes, and the capability of pattern maintenance or reproducibility. Defining this robustness property is a challenging task,…

Molecular Networks · Quantitative Biology 2007-10-24 Madalena Chave , Eduardo D. Sontag , Anirvan M. Sengupta

Protein expression levels optimize cell fitness: Too low an expression level of essential proteins will slow growth by compromising essential processes; whereas overexpression slows growth by increasing the metabolic load. This trade-off…

Biological Physics · Physics 2024-08-23 H. James Choi , Teresa W. Lo , Kevin J. Cutler , Dean Huang , W. Ryan Will , Paul A. Wiggins

The spectrum and scale of fluctuations in protein structures affect the range of cell phenomena, including stability of protein structures or their fragments, allosteric transitions and energy transfer. The study presents a…

Biomolecules · Quantitative Biology 2015-05-13 Anatoly M. Ruvinsky , Ilya A. Vakser

A Profile Mixture Model is a model of protein evolution, describing sequence data in which sites are assumed to follow many related substitution processes on a single evolutionary tree. The processes depend in part on different amino acid…

Populations and Evolution · Quantitative Biology 2020-07-07 Samaneh Yourdkhani , Elizabeth S. Allman , John A. Rhodes

To determine the 3D conformation of proteins is a necessity to understand their functions or interactions with other molecules. It is commonly admitted that, when proteins fold from their primary linear structures to their final 3D…

Biomolecules · Quantitative Biology 2013-06-07 Jacques M. Bahi , Wojciech Bienia , Nathalie Côté , Christophe Guyeux