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We introduce a computational method to discover polymorphs in molecular crystals at finite temperature. The method is based on reproducing the crystallization process starting from the liquid and letting the system discover the relevant…

Chemical Physics · Physics 2020-04-10 Pablo M. Piaggi , Michele Parrinello

We consider a generalization of the discrete-time Self Healing Umbrella Sampling method, which is an adaptive importance technique useful to sample multimodal target distributions. The importance function is based on the weights (namely the…

Probability · Mathematics 2017-09-04 Gersende Fort , Benjamin Jourdain , Tony Lelièvre , Gabriel Stoltz

A coarse-grained variational model is used to investigate the polymer dynamics of barrier crossing for a diverse set of two-state folding proteins. The model gives reliable folding rate predictions provided excluded volume terms that induce…

Biomolecules · Quantitative Biology 2009-11-13 Xianghong Qi , John J. Portman

The accurate sampling of protein dynamics is an ongoing challenge despite the utilization of High-Performance Computers (HPC) systems. Utilizing only "brute force" MD simulations requires an unacceptably long time to solution. Adaptive…

Quantitative Methods · Quantitative Biology 2020-09-25 Eugen Hruska , Vivekanandan Balasubramanian , Hyungro Lee , Shantenu Jha , Cecilia Clementi

Metadynamics is an established sampling method aimed at reconstructing the free-energy surface relative to a set of appropriately chosen collective variables. In standard metadynamics the free-energy surface is filled by the addition of…

Statistical Mechanics · Physics 2012-07-11 Davide Branduardi , Giovanni Bussi , Michele Parrinello

A statistical mechanical theory is presented to predict the effects of macromolecular crowding on protein association equilibria, accounting for both excluded volume and attractive interactions between proteins and crowding molecules.…

Soft Condensed Matter · Physics 2015-06-11 Young C. Kim , Jeetain Mittal

While recent advances in AI have transformed protein structure prediction, protein function is also strongly influenced by the thermodynamic and kinetic features encoded in its underlying free-energy surface. Here, we propose a…

Biological Physics · Physics 2026-04-29 Alexander Zhilkin , Muralika Medaparambath , Dan Mendels

Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and…

Soft Condensed Matter · Physics 2007-12-06 Michael Bachmann , Wolfhard Janke

Equations that govern the temperature-dependence of the rate constants, Gibbs energies,enthalpies, entropies and heat capacities of activation for folding and unfolding of spontaneously-folding fixed two-state systems have been derived…

Soft Condensed Matter · Physics 2016-05-11 Robert S. Sade

Controlling polymorphism in molecular crystals is crucial in the pharmaceutical, dye, and pesticide industries. However, its theoretical description is extremely challenging, due to the associated long timescales ($ > 1 \, \mu s$). We…

Chemical Physics · Physics 2023-02-09 Oren Elishav , Roy Podgaetsky , Olga Meikler , Barak Hirshberg

Many signalling functions in molecular biology require proteins bind to substrates such as DNA in response to environmental signals such as the simultaneous binding to a small molecule. Examples are repressor proteins which may transmit…

Biomolecules · Quantitative Biology 2009-11-10 Rhoda J. Hawkins , Thomas C. B. McLeish

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

We describe a method that focuses sampling effort on a user-defined selection of a large system, which can lead to substantial decreases in computational effort by speeding up the calculation of nonbonded interactions. A naive approach can…

Statistical Mechanics · Physics 2023-08-28 Joshua Fass , Forrest York , Matthew Wittmann , Joseph Kaus , Yutong Zhao

The conformational dynamics of a single protein molecule in a shear flow is investigated using Brownian dynamics simulations. A structure-based coarse grained model of a protein is used. We consider two proteins, ubiquitin and integrin, and…

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

Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this…

Chemical Physics · Physics 2023-07-31 Gianmarco Lazzeri , Hendrik Jung , Peter G. Bolhuis , Roberto Covino

Elastic network models (ENM) and constraint-based, topological rigidity analysis are two distinct, coarse-grained approaches to study conformational flexibility of macromolecules. In the two decades since their introduction, both have…

Biomolecules · Quantitative Biology 2018-02-27 Dominik Budday , Sigrid Leyendecker , Henry van den Bedem

A variety of enhanced sampling methods predict multidimensional free energy landscapes associated with biological and other molecular processes as a function of a few selected collective variables (CVs). The accuracy of these methods is…

Computational Physics · Physics 2024-04-09 Lukas Müllender , Andrea Rizzi , Michele Parrinello , Paolo Carloni , Davide Mandelli

We investigate the effect of macromolecular crowding on protein folding, using purely repulsive crowding particles and a self-organizing polymer model of protein folding. We find that the thermodynamics of folding for typical alpha-, beta-…

Soft Condensed Matter · Physics 2009-02-27 Jeetain Mittal , Robert B. Best

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 elastic network (EN) is a prime model that describes the long-time dynamics of biomolecules. However, the use of harmonic potentials renders this model insufficient for studying large conformational changes of proteins (e.g. stretching…

Biological Physics · Physics 2018-11-06 A. B. Poma , M. S. Li , P. E. Theodorakis