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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

Energetic correlations due to polymeric constraints and the locality of interactions, in conjunction with the apriori specification of the existence of a particularly low energy state, provides a method of introducing the aspect of minimal…

Condensed Matter · Physics 2009-10-28 Steven S. Plotkin , Jin Wang , Peter G. Wolynes

A four states phase diagram for protein folding as a function of temperature and solvent quality is derived from an improved 2-d lattice model taking into account the temperature dependence of the hydrophobic effect. The phase diagram…

Statistical Mechanics · Physics 2009-11-11 Olivier Collet

We present a simple model of protein folding dynamics that captures key qualitative elements recently seen in all-atom simulations. The goals of this theory are to serve as a simple formalism for gaining deeper insight into the physical…

Biological Physics · Physics 2015-05-19 Vijay S. Pande

In order to elucidate the role of the native state topology and the stability of subdomains in protein folding, we investigate free energy landscape of human lysozyme, which is composed of two subdomains, by Monte Carlo simulations. A…

Biomolecules · Quantitative Biology 2007-05-23 Hiroo Kenzaki , Macoto Kikuchi

Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…

Biological Physics · Physics 2013-07-22 Ji Xu , Mengzhi Han , Ying Ren , Jinghai Li

Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small fast folding proteins. To investigate the extent of the…

Statistical Mechanics · Physics 2007-05-23 Cecilia Clementi , Hugh Nymeyer , Jose' Nelson Onuchic

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

The statistical properties of protein folding within the {\phi}^4 model are investigated. The calculation is performed using statistical mechanics and path integral method. In particular, the evolution of heat capacity in term of…

Biological Physics · Physics 2013-09-03 M. Januar , A. Sulaiman , L. T. Handoko

Natural proteins fold to a unique, thermodynamically dominant state. Modeling of the folding process and prediction of the native fold of proteins are two major unsolved problems in biophysics. Here, we show successful all-atom ab initio…

Biomolecules · Quantitative Biology 2007-05-23 Jae Shick Yang , William W. Chen , Jeffrey Skolnick , Eugene I. Shakhnovich

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

In spite of decades of research, much remains to be discovered about folding: the detailed structure of the initial (unfolded) state, vestigial folding instructions remaining only in the unfolded state, the interaction of the molecule with…

Biological Physics · Physics 2018-11-26 Walter A. Simmons

The dynamics of two 12-monomer heteropolymers on the square lattice is studied exactly within the master equation approach. The time evolution of the occupancy of the native state is determined. At low temperatures, the median folding time…

Statistical Mechanics · Physics 2009-09-25 Marek Cieplak , Malte Henkel , Jayanth R. Banavar

Developing accurate and efficient coarse-grained representations of proteins is crucial for understanding their folding, function, and interactions over extended timescales. Our methodology involves simulating proteins with molecular…

Biomolecules · Quantitative Biology 2023-10-11 Carles Navarro , Maciej Majewski , Gianni de Fabritiis

We argue that protein native state structures reside in a novel "phase" of matter which confers on proteins their many amazing characteristics. This phase arises from the common features of all globular proteins and is characterized by a…

Biomolecules · Quantitative Biology 2012-04-13 Jayanth R. Banavar , Trinh X. Hoang , Flavio Seno , Antonio Trovato , Amos Maritan

We have analyzed dynamics on the complex free energy landscape of protein folding in the FOLD-X model, by calculating for each state of the system the mean first passage time to the folded state. The resulting kinetic map of the folding…

Statistical Mechanics · Physics 2009-11-10 M. A. Micheelsen , C. Rischel , J. Ferkinghoff-Borg , R. Guerois , L. Serrano

Local minima and the saddle points separating them in the energy landscape are known to dominate the dynamics of biopolymer folding. Here we introduce a notion of a "folding funnel" that is concisely defined in terms of energy minima and…

Biomolecules · Quantitative Biology 2009-11-13 Konstantin Klemm , Christoph Flamm , Peter F. Stadler

We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…

Disordered Systems and Neural Networks · Physics 2008-02-03 T. Garel , H. Orland , E. Pitard

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

It is shown that a small subset of modes which are likely to be involved in protein functional motions of large amplitude can be determined by retaining the most robust normal modes obtained using different protein models. This result…

Biomolecules · Quantitative Biology 2007-05-23 Samuel Nicolay , Yves-Henri Sanejouand