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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

A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…

Disordered Systems and Neural Networks · Physics 2007-05-23 Steven S. Plotkin , Jose N. Onuchic

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

One of the main concerns of Anfinsen was to reveal the connection between the amino acid sequence and their biologically active conformation. This search gave rise to two crucial questions in structural biology, namely, why the proteins…

Biomolecules · Quantitative Biology 2022-10-12 Jorge A. Vila

A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical…

Biomolecules · Quantitative Biology 2009-11-13 Gregg Lois , Jerzy Blawzdziewicz , Corey S. O'Hern

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can…

Disordered Systems and Neural Networks · Physics 2009-10-31 Steven S. Plotkin , Jose N. Onuchic

Extensive Monte Carlo folding simulations for four proteins of various structural classes are carried out, using a single atomistic potential. In all cases, collapse occurs at a very early stage, and proteins fold into their native-like…

Statistical Mechanics · Physics 2009-11-10 Seung-Yeon Kim , Julian Lee , Jooyoung Lee

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

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 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 protein folding problem is stated and a list of properties that do not depend upon specific molecules is compiled and analyzed. The relationship of this analysis to future simulations is emphasized. The choice of power and time as…

Biological Physics · Physics 2017-09-26 Walter A. Simmons

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

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

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

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

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

Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to…

Soft Condensed Matter · Physics 2007-05-23 R. A. Broglia , G. Tiana , H. E. Roman

One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…

Biomolecules · Quantitative Biology 2026-01-13 Jorge Vila

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

Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins.…

Biomolecules · Quantitative Biology 2014-04-01 Ernesto A. Roman , F. Luis Gonzalez Flecha
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