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Finding representative reaction pathways is necessary for understanding mechanisms of molecular processes, but is considered to be extremely challenging. We propose a new method to construct reaction paths based on mean first-passage times.…

Chemical Physics · Physics 2015-06-26 Sanghyun Park , Klaus Schulten

A quantitative model of the mobility of functionalized particles at the interface is pivotal to understanding important systems in biology and nanotechnology. In this work, we investigate the emerging dynamics of particles anchored through…

Soft Condensed Matter · Physics 2024-06-19 Janna Lowensohn , Laurie Stevens , Daniel Goldstein , Bortolo Matteo Mognetti

The dynamical characterization of proteins is crucial to understand protein function. From a microscopic point of view, protein dynamics is governed by the local atomic interactions that, in turn, trigger the functional conformational…

Biomolecules · Quantitative Biology 2010-01-21 Francesco Rao

Proteins need to selectively interact with specific targets among a multitude of similar molecules in the cell. But despite a firm physical understanding of binding interactions, we lack a general theory of how proteins evolve high…

Biomolecules · Quantitative Biology 2022-09-28 John M McBride , Jean-Pierre Eckmann , Tsvi Tlusty

We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…

Statistical Mechanics · Physics 2007-05-23 Nikolay V. Dokholyan , Eugene I. Shakhnovich

The fundamental law for protein folding is the Thermodynamic Principle: the amino acid sequence of a protein determines its native structure and the native structure has the minimum Gibbs free energy. If all chemical problems can be…

Biomolecules · Quantitative Biology 2012-04-10 Yi Fang

We present a Monte Carlo study of a model protein with 54 amino acids that folds directly to its native three-helix-bundle state without forming any well-defined intermediate state. The free-energy barrier separating the native and unfolded…

Biomolecules · Quantitative Biology 2009-11-10 Giorgio Favrin , Anders Irbäck , Björn Samuelsson , Stefan Wallin

Various biological sensory systems exhibit a response to a relative change of the stimulus, often referred to as fold-change detection. In the last few years fold-change detecting mechanisms, based on transcriptional networks, have been…

Biological Physics · Physics 2014-02-21 Wouter Buijsman , Michael Sheinman

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

Equilibrium and out-of-equilibrium transitions of an off-lattice protein model have been identified and studied. In particular, the out-of-equilibrium dynamics of the protein undergoing mechanical unfolding is investigated, and by using a…

Soft Condensed Matter · Physics 2010-07-14 A. Imparato , S. Luccioli , A. Torcini

The dynamics of biological polymers, including proteins, RNA, and DNA, occur in very high-dimensional spaces. Many naturally-occurring polymers can navigate a vast phase space and rapidly find their lowest free energy (folded) state. Thus,…

Computational Physics · Physics 2024-06-19 Frederico Campos Freitas , Sandra Byju , Asem Hassan , Ronaldo Junio de Oliveira , Paul C. Whitford

Cotranslational folding depends on the folding speed and stability of the nascent protein. It remains difficult, however, to predict which proteins cotranslationally fold. Here, we simulate evolution of model proteins to investigate how…

Biomolecules · Quantitative Biology 2020-10-28 Victor Zhao , William M. Jacobs , Eugene I. Shakhnovich

Bursting is a phenomenon found in a variety of physical and biological systems. For example, in neuroscience, bursting is believed to play a key role in the way information is transferred in the nervous system. In this work, we propose a…

Neurons and Cognition · Quantitative Biology 2016-05-31 Maria Luisa Saggio , Andreas Spiegler , Christophe Bernard , Viktor K. Jirsa

A generic model of a random polypeptide chain, with discrete torsional degrees of freedom and Hookean springs connecting pairs of hydrophobic residues, reproduces the energy probability distribution of real proteins over a very large range…

Soft Condensed Matter · Physics 2007-05-23 Erkan Tuzel , Ayse Erzan

Cooperativity is a hallmark of proteins, many of which show a modular architecture comprising discrete structural domains. Detecting and describing dynamic couplings between structural regions is difficult in view of the many-body nature of…

Biological Physics · Physics 2015-02-03 Olga Kononova , Lee Jones , Valeri Barsegov

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly…

Biomolecules · Quantitative Biology 2024-09-04 Bowen Jing , Bonnie Berger , Tommi Jaakkola

Automated identification of protein conformational states from simulation of an ensemble of structures is a hard problem because it requires teaching a computer to recognize shapes. We adapt the naive Bayes classifier from the machine…

Computational Physics · Physics 2020-12-02 David M. Rogers

Many biological processes are supported by special molecules, called motor proteins or molecular motors, that transport cellular cargoes along linear protein filaments and can reversibly associate to their tracks. Stimulated by these…

Statistical Mechanics · Physics 2021-11-17 Akriti Jindal , Anatoly B. Kolomeisky , Arvind Kumar Gupta

A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven different helix bundle proteins. The protocol, which includes…

Biomolecules · Quantitative Biology 2009-11-11 Isaac A. Hubner , Eric J. Deeds , Eugene I. Shakhnovich

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