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In the past years, the folding kinetics of many small single-domain proteins has been characterized by mutational Phi-value analysis. In this article, a simple, essentially parameter-free model is introduced which derives folding routes…

Biomolecules · Quantitative Biology 2007-05-23 Thomas R. Weikl

We present a novel machine learning approach to understanding conformation dynamics of biomolecules. The approach combines kernel-based techniques that are popular in the machine learning community with transfer operator theory for…

Computational Physics · Physics 2019-01-24 Stefan Klus , Andreas Bittracher , Ingmar Schuster , Christof Schütte

Kinetics of folding of a protein held in a force-clamp are compared to an unconstrained folding. The comparison is made within a simple topology-based dynamical model of ubiquitin. We demonstrate that the experimentally observed variations…

Biomolecules · Quantitative Biology 2009-11-13 Marek Cieplak , Piotr Szymczak

A theoretical analysis of the unfolding pathway of simple modular proteins in length- controlled pulling experiments is put forward. Within this framework, we predict the first module to unfold in a chain of identical units, emphasizing the…

Soft Condensed Matter · Physics 2018-07-03 Carlos A. Plata , Zackary N. Scholl , Piotr E. Marszalek , A. Prados

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a…

Biomolecules · Quantitative Biology 2023-11-27 Igor Melnyk , Aurelie Lozano , Payel Das , Vijil Chenthamarakshan

Mechanical unfolding of polyproteins by force spectroscopy provides valuable insight into their free energy landscapes. Most phenomenological models of the unfolding process are two-state and/or one dimensional, with the details of the…

Biological Physics · Physics 2015-06-26 Daniel K. West , Emanuele Paci , Peter D. Olmsted

We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a…

Biological Physics · Physics 2013-08-13 Jacek Wabik , Sebastian Kmiecik , Dominik Gront , Maksim Kouza , Andrzej Kolinski

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

Time-resolved single-molecule biophysical experiments yield data that contain a wealth of dynamic information, in addition to the equilibrium distributions derived from histograms of the time series. In typical force spectroscopic setups…

Biomolecules · Quantitative Biology 2011-07-14 Michael Hinczewski , Yann von Hansen , Roland R. Netz

Protein folding and design are major biophysical problems, the solution of which would lead to important applications especially in medicine. Here a novel protein model capable of simultaneously provide quantitative protein design and…

Biological Physics · Physics 2015-06-22 Ivan Coluzza

Protein folding, peptide aggregation and crystallization, as well as adsorption of molecules on soft or solid substrates have an essential feature in common: In all these processes, structure formation is guided by a collective, cooperative…

Statistical Mechanics · Physics 2009-02-12 Michael Bachmann , Wolfhard Janke

Energy evaluation using fast Fourier transforms enables sampling billions of putative complex structures and hence revolutionized rigid protein-protein docking. However, in current methods efficient acceleration is achieved only in either…

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

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 offer simple solutions to three kinematic problems that occur in the folding of proteins. We show how to construct suitably local elementary Monte Carlo moves, how to close a loop, and how to fold a loop without breaking the bond that…

Biological Physics · Physics 2016-09-08 Sean Cahill , Michael Cahill , Kevin Cahill

The dynamic nature of proteins, influenced by ligand interactions, is essential for comprehending protein function and progressing drug discovery. Traditional structure-based drug design (SBDD) approaches typically target binding sites with…

Biomolecules · Quantitative Biology 2025-03-07 Xiangxin Zhou , Yi Xiao , Haowei Lin , Xinheng He , Jiaqi Guan , Yang Wang , Qiang Liu , Feng Zhou , Liang Wang , Jianzhu Ma

To what extent do general features of folding/unfolding kinetics of small globular proteins follow from their thermodynamic properties? To address this question, we investigate a new simplifed protein chain model that embodies a cooperative…

Soft Condensed Matter · Physics 2007-05-23 Huseyin Kaya , Hue Sun Chan

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

Different models such as diffusion-collision and nucleation-condensation have been used to unravel how secondary and tertiary structures form during protein folding. However, a simple mechanism based on physical principles that provide an…

Biomolecules · Quantitative Biology 2014-10-15 Leandro P. Nadaletti , Beatriz S. L. P. de Lima , Solange Guimarães

We propose a general theory to describe the distribution of protein-folding transition paths. We show that transition paths follow a predictable sequence of high-free-energy transient states that are separated by free-energy barriers. Each…

Biomolecules · Quantitative Biology 2016-09-21 William M. Jacobs , Eugene I. Shakhnovich