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The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Biomolecules · Quantitative Biology 2015-03-13 Debora S. Marks , Lucy J. Colwell , Robert Sheridan , Thomas A. Hopf , Andrea Pagnani , Riccardo Zecchina , Chris Sander

Most amino acids are encoded by multiple synonymous codons. For an amino acid, some of its synonymous codons are used much more rarely than others. Analyses of positions of such rare codons in protein sequences revealed that rare codons can…

Molecular Networks · Quantitative Biology 2019-07-09 Khalique Newaz , Gabriel Wright , Jacob Piland , Jun Li , Patricia Clark , Scott Emrich , Tijana Milenkovic

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

While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of…

Biomolecules · Quantitative Biology 2009-11-10 R. A. Broglia , G. Tiana

The idea of the evolution of the genetic code from the CG to the CGUA alphabet has been developed further. The assumption of the originally triplet structure of the genetic code has been substantiated. The hypothesis of the emergence of…

Biomolecules · Quantitative Biology 2008-04-29 Denis A. Semenov

The idea that structural disorder might be a novel mechanism of protein interaction is widespread in the Literature, although the number of statistically significant structural studies supporting this is surprisingly low. At variance with…

Disordered Systems and Neural Networks · Physics 2021-03-01 Beatriz Seoane , Alessandra Carbone

The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…

Biomolecules · Quantitative Biology 2008-06-25 Konstantin B. Zeldovich , Eugene I. Shakhnovich

A central challenge in the study of protein evolution is the identification of historic amino acid sequence changes responsible for creating novel functions observed in present-day proteins. To address this problem, we developed a new…

Genomics · Quantitative Biology 2014-06-13 Victor Hanson-Smith , Christopher Baker , Alexander Johnson

Proteins are the major building blocks of life, and actuators of almost all chemical and biophysical events in living organisms. Their native structures in turn enable their biological functions which have a fundamental role in drug design.…

Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…

Biomolecules · Quantitative Biology 2025-05-26 Ezequiel A. Galpern , Federico Caamaño , Diego U. Ferreiro

The conformations available to polypeptides are determined by the interatomic forces acting on the peptide units, whereby backbone torsion angles are restricted as described by the Ramachandran plot. Although typical proteins are composed…

Biomolecules · Quantitative Biology 2013-02-11 Anil Korkut , Wayne A Hendrickson

Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here we ask the question what makes a protein promiscuous, i.e., prone to non-specific interactions, and structurally disordered.…

Biomolecules · Quantitative Biology 2011-05-10 Ariel Afek , Eugene I. Shakhnovich , David B. Lukatsky

Proteins are fundamental biological entities that play a key role in life activities. The amino acid sequences of proteins can be folded into stable 3D structures in the real physicochemical world, forming a special kind of…

Machine Learning · Computer Science 2023-01-04 Lirong Wu , Yufei Huang , Haitao Lin , Stan Z. Li

Multiple phenotypic protein expressions arising from one genome represent variations in the protein relative abundance and their stoichiometry. A lack of definite compositional parts challenges the modeling of protein megacomplexes and…

Biomolecules · Quantitative Biology 2026-02-24 Jiayi Wang , Jules Nde , Andrei G. Gasic , Jacob Haseley , Margaret S. Cheung

The 21st century is presenting humankind with unprecedented environmental and medical challenges. The ability to design novel proteins tailored for specific purposes could transform our ability to respond timely to these issues. Recent…

Biomolecules · Quantitative Biology 2022-08-24 Noelia Ferruz , Birte Höcker

Protein-protein interactions (protein functionalities) are mediated by water, which compacts individual proteins and promotes close and temporarily stable large-area protein-protein interfaces. Proteins are peptide chains decorated by amino…

Soft Condensed Matter · Physics 2008-02-26 J. C. Phillips

Complex systems with tightly coadapted parts frequently appear in living systems and are difficult to account for through Darwinian evolution, that is random variation and natural selection, if the constituent parts are independently coded…

Adaptation and Self-Organizing Systems · Physics 2007-05-23 John F. McGowan , Ph. D

What are proteins made from, as the working parts of the living cells protein machines? To answer this question, we need a technology to disassemble proteins onto elementary func-tional details and to prepare lumped description of such…

Biomolecules · Quantitative Biology 2007-11-05 A. N. Gorban , M. Kudryashev , T. Popova

A fundamental question for evolutionary biology is why rates of evolution vary dramatically between proteins. Perhaps surprisingly, it is controversial how much a protein's functional importance affects its rate of evolution. In most…

Populations and Evolution · Quantitative Biology 2009-09-20 Ryan N. Gutenkunst

Just as physicists strive to develop a TOE (theory of everything), which explains and unifies the physical laws of the universe, the life-scientist wishes to uncover the TOE as it relates to cellular systems. This can only be achieved with…

Quantitative Methods · Quantitative Biology 2009-11-04 Kyung Dae Ko , Yoojin Hong , Gaurav Bhardwaj , Teresa M. Killick , Damian B. van Rossum , Randen L. Patterson
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