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Proteins created by combinatorial methods in vitro are an important source of information for understanding sequence-structure-function relationships. Alignments of folded proteins from combinatorial libraries can be analyzed using methods…

Biomolecules · Quantitative Biology 2007-05-23 Jeffrey B. Endelman , Jesse D. Bloom , Christopher R. Otey , Marco Landwehr , Frances H. Arnold

The principles underlying protein folding remains one of Nature's puzzles with important practical consequences for Life. An approach that has gathered momentum since the late 1990's, looks at protein hetero-polymers and their folding…

Computational Engineering, Finance, and Science · Computer Science 2011-10-05 Susan Khor

A geometric analysis of the global properties of the energy landscape of a minimalistic model of a polypeptide is presented, which is based on the relation between dynamical trajectories and geodesics of a suitable manifold, whose metric is…

Statistical Mechanics · Physics 2009-11-13 Lorenzo N. Mazzoni , Lapo Casetti

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

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

Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…

Quantitative Methods · Quantitative Biology 2018-01-04 Sam Sinai , Eric Kelsic , George M. Church , Martin A. Nowak

In this Communication we present statistical analysis of conservation profiles in families of homologous sequences for nine proteins whose folding nucleus was determined by protein engineering methods. We show that in all but one protein…

Biological Physics · Physics 2007-05-23 Leonid Mirny , Eugene Shakhnovich

An all-atom model of proteins is used to show that the same sequence of amino acids can have many alternative structures, that are very distant from, and that can be as stable as, the corresponding native structure. Such alternative…

Biological Physics · Physics 2008-02-11 Leonor Cruzeiro

Many native structures of proteins accomodate complex topological motifs such as knots, lassos, and other geometrical entanglements. How proteins can fold quickly even in the presence of such topological obstacles is a debated question in…

Soft Condensed Matter · Physics 2020-10-07 Federico Norbiato , Flavio Seno , Antonio Trovato , Marco Baiesi

While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learnt how to extract this information so as to predict the detailed, biological active, three-dimensional structure of…

Condensed Matter · Physics 2007-05-23 R. A. Broglia , G. Tiana

The dynamics of folding of proteins is studied by means of a phenomenological master equation. The energy distribution is taken as a truncated exponential for the misfolded states plus a native state sitting below the continuum. The…

Soft Condensed Matter · Physics 2007-05-23 Estelle Pitard , Henri Orland

We investigate the folding behavior of protein sequences by numerically studying all sequences with maximally compact lattice model through exhaustive enumeration. We get the prion-like behavior of protein folding. Individual proteins…

Biomolecules · Quantitative Biology 2014-11-18 Yong-Yun Ji , You-Quan Li , Jun-Wen Mao , Xiao-Wei Tang

Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function impose structural and functional constraints on each residue site. Selective constraints on residue sites are…

Biomolecules · Quantitative Biology 2013-01-18 Sanzo Miyazawa

The classical approach to protein folding inspired by statistical mechanics avoids the high dimensional structure of the conformation space by using effective coordinates. Here we introduce a network approach to capture the statistical…

Biomolecules · Quantitative Biology 2007-05-23 Erzsebet Ravasz , S. Gnanakaran , Zoltan Toroczkai

We discuss a model of protein conformations where the conformations are combinations of short fragments from some small set. For these fragments we consider a distribution of frequencies of occurrence of pairs (sequence of amino acids,…

Biomolecules · Quantitative Biology 2016-07-05 S. V. Kozyrev

Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…

Biomolecules · Quantitative Biology 2023-11-13 A. Zambon , R. Zecchina , G. Tiana

A microscopic theory of the free energy barriers and folding routes for minimally frustrated proteins is presented, greatly expanding on the presentation of the variational approach outlined previously [J. J. Portman, S. Takada, P. G.…

Soft Condensed Matter · Physics 2009-10-31 John J. Portman , Shoji Takada , Peter G. Wolynes

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

The prediction of the three-dimensional structures of the native state of proteins from the sequences of their amino acids is one of the most important challenges in molecular biology. An essential ingredient to solve this problem within…

Statistical Mechanics · Physics 2007-05-23 Cristian Micheletti , Flavio Seno , Jayanth Banavar , Amos Maritan

A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…

Biomolecules · Quantitative Biology 2018-08-09 William M. Jacobs , Eugene I. Shakhnovich