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A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…

Biomolecules · Quantitative Biology 2026-01-09 Myeongsang Lee , Lauren L. Porter

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, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…

Biomolecules · Quantitative Biology 2007-05-23 Eric J. Deeds , Eugene I. Shakhnovich

Proteins are the "work horses" in biological systems. In almost all functions specific proteins are involved. They control molecular transport processes, stabilize the cell structure, enzymatically catalyze chemical reactions; others act as…

Statistical Mechanics · Physics 2009-02-18 Michael Bachmann , Wolfhard Janke

These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…

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

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

The native state structures of globular proteins are stable and well-packed indicating that self-interactions are favored over protein-solvent interactions under folding conditions. We use this as a guiding principle to derive the geometry…

Biomolecules · Quantitative Biology 2021-07-14 Tatjana Škrbić , Amos Maritan , Achille Giacometti , George D. Rose , Jayanth R. Banavar

Protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use only sequence information to go beyond predicting native structures and global stability…

Biomolecules · Quantitative Biology 2025-07-02 Ezequiel A. Galpern , Ernesto A. Roman , Diego U. Ferreiro

Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we…

Biomolecules · Quantitative Biology 2016-06-20 Yuanzhao Zhang , Jeffrey K Weber , Ruhong Zhou

Protein structures are a very special class among all possible structures. It was suggested that a ``designability principle'' plays a crucial role in nature's selection of protein sequences and structures. Here we provide a theoretical…

Statistical Mechanics · Physics 2009-10-30 Hao Li , Chao Tang , Ned S. Wingreen

A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same…

Soft Condensed Matter · Physics 2007-05-23 Nan-yow Chen

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

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the…

Biological Physics · Physics 2008-11-24 Pablo Echenique

Predicting the three-dimensional (3D) functional structures of proteins remains an important computational milestone in molecular biology to be achieved. This feat is hinged on a clear understanding of the mechanism which proteins use to…

Biomolecules · Quantitative Biology 2019-11-28 Samuel Nkrumah

The protein folding problem must ultimately be solved on all length scales from the atomic up through a hierarchy of complicated structures. By analyzing the stability of the folding process using physics and mathematics, this paper shows…

Biological Physics · Physics 2015-05-28 Walter Simmons , Joel L. Weiner

The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…

Biomolecules · Quantitative Biology 2020-01-08 Thomas R. Weikl

A fascinating and open question challenging biochemistry, physics and even geometry is the presence of highly regular motifs such as alpha-helices in the folded state of biopolymers and proteins. Stimulating explanations ranging from…

Statistical Mechanics · Physics 2009-10-31 Amos Maritan , Cristian Micheletti , Jayanth R. Banavar

Two proteins, one belonging to the mainly alpha class and the other belonging to the alpha/beta class, are selected to test a kinetic mechanism for protein folding. Targeted molecular dynamics is applied to generate folding pathways for…

Biological Physics · Physics 2011-01-04 Leonor Cruzeiro

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

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques,…

Biomolecules · Quantitative Biology 2019-10-07 Simona Cocco , Christoph Feinauer , Matteo Figliuzzi , Remi Monasson , Martin Weigt
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