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We discuss recent theoretical developments in the study of simple lattice models of proteins. Such models are designed to understand general features of protein structures and mechanism of folding. Among the topics covered are (i) the use…

Soft Condensed Matter · Physics 2007-05-23 D. Thirumalai , D. K. Klimov

A simple lattice model, recently introduced as a generalization of the Wako--Sait\^o model of protein folding, is used to investigate the properties of widely studied molecules under external forces. The equilibrium properties of the model…

Soft Condensed Matter · Physics 2007-10-16 A. Imparato , A. Pelizzola , M. Zamparo

We review theoretical approaches, experiments and numerical simulations that have been recently proposed to investigate the folding problem in single-domain proteins. From a theoretical point of view, we emphasize the energy landscape…

Biological Physics · Physics 2008-10-20 Ivan Junier , Felix Ritort

Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an…

Biological Physics · Physics 2017-01-24 Changbong Hyeon , Michael Hinczewski , D. Thirumalai

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

This letter explores how a reinterpretation of the generalized uncertainty principle as an effective variation of Planck's constant provides a physical explanation for a number of fundamental quantities and couplings. In this context, a…

General Physics · Physics 2024-09-02 Ahmed Farag Ali , Jonas Mureika , Elias C. Vagenas , Ibrahim Elmashad

Recent advancements in machine learning have emphasized the need for transparency in model predictions, particularly as interpretability diminishes when using increasingly complex architectures. In this paper, we propose leveraging…

Machine Learning · Computer Science 2025-07-18 Chenrui Zhu , Louenas Bounia , Vu Linh Nguyen , Sébastien Destercke , Arthur Hoarau

Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To…

Biomolecules · Quantitative Biology 2025-02-10 R. Gonzalo Parra , Elizabeth A. Komives , Peter G. Wolynes , Diego U. Ferreiro

Activated processes such as protein unfolding are highly sensitive to heterogeneity in the environment. We study a highly simplified model of a protein in a random heterogeneous environment, a model of the in vivo environment. It is found…

Biomolecules · Quantitative Biology 2009-11-10 Richard P. Sear

Molecular dynamics simulations of folding in an off-lattice protein model reveal a nucleation scenario, in which a few well-defined contacts are formed with high probability in the transition state ensemble of conformations. Their…

Statistical Mechanics · Physics 2009-09-25 Nikolay V. Dokholyan , Sergey V. Buldyrev , H. Eugene Stanley , Eugene I. Shakhnovich

We discuss several aspects of creation of adequate mathematical models in other sciences. In particular, many difficulties stem from great complexity of the source systems and the presence of a variety of uncertain factors. We illustrate…

Optimization and Control · Mathematics 2021-02-19 I. V. Konnov

Many aspects of the study of protein folding and dynamics have been affected by the recent advances in machine learning. Methods for the prediction of protein structures from their sequences are now heavily based on machine learning tools.…

Biological Physics · Physics 2019-11-25 Frank Noé , Gianni De Fabritiis , Cecilia Clementi

Protein evolution underpins life, and understanding its behavior as a system is of great importance. However, our current models of protein evolution are arguably too simplistic to allow quantitative interpretation and prediction of…

The 20th century has revealed two important limitations of scientific knowledge. On the one hand, the combination of Poincar\'e's nonlinear dynamics and Heisenberg's uncertainty principle leads to a world picture where physical reality is,…

History and Philosophy of Physics · Physics 2013-04-10 Fernando Sols

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

The famous Laplace's Demon is not only of strict physical determinism, but also related to the power of differential equations. When deterministically extended structures are taken into consideration, it is admissible that fractals are…

Dynamical Systems · Mathematics 2018-03-21 Marat Akhmet , Mehmet Onur Fen , Ejaily Milad Alejaily

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native…

Biomolecules · Quantitative Biology 2016-10-20 Sophie E. Jackson , Antonio Suma , Cristian Micheletti

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

We solve a model that takes into account entropic barriers, frustration, and the organization of a protein-like molecule. For a chain of size $M$, there is an effective folding transition to an ordered structure. Without frustration, this…

Condensed Matter · Physics 2009-10-28 Carlos J. Camacho

As far as human perceptions and rational thinking are concerned, contradictions constitute a non negligible part of our reality. We often refer to these phenomena, in a more informal way, as the chicken or the egg causality dilemma.…

Biological Physics · Physics 2014-04-24 Akos Dobay