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Proteins are a matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with multifarious biochemistry. But it is also an instantiation along an evolutionary trajectory determined by the function…

Biomolecules · Quantitative Biology 2019-09-04 Jean-Pierre Eckmann , Jacques Rougemont , Tsvi Tlusty

Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural…

Condensed Matter · Physics 2009-10-28 Hao Li , Robert Helling , Chao Tang , Ned Wingreen

Simple two-state folding kinetics of many small single-domain proteins are characterized by chevron plots with linear folding and unfolding arms consistent with a two-state description of equilibrium thermodynamics. This phenomenon is…

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

Using a structure-based coarse-grained model of proteins, we study the mechanism of unfolding of knotted proteins through heating. We find that the dominant mechanisms of unfolding depend on the temperature applied and are generally…

Biomolecules · Quantitative Biology 2017-01-23 Yani Zhao , Mateusz Chwastyk , Marek Cieplak

We present a computational scheme for predicting the ligands that bind to a pocket of known structure. It is based on the generation of a general abstract representation of the molecules, which is invariant to rotations, translations and…

Chemical Physics · Physics 2024-05-09 R. Beccaria , A. Lazzeri , G. Tiana

When described by a low-dimensional reaction coordinate, the rates of protein folding are determined by a subtle interplay between free-energy barriers and friction. While it is commonplace to extract free-energy profiles from molecular…

Soft Condensed Matter · Physics 2022-10-24 Benjamin A. Dalton , Cihan Ayaz , Lucas Tepper , Roland R. Netz

The phase behavior of charged rods in the presence of inter-rod linkers is studied theoretically as a model for the equilibrium behavior underlying the organization of actin filaments by linker proteins in the cytoskeleton. The presence of…

Soft Condensed Matter · Physics 2016-08-31 Itamar Borukhov , Robijn F. Bruinsma , William M. Gelbart , Andrea J. Liu

Perturbing a Go model towards a realistic protein Hamiltonian by adding non-native interactions, we find that the folding rate is in general enhanced as ruggedness is initially increased, as long as the protein is sufficiently large and…

Disordered Systems and Neural Networks · Physics 2007-05-23 Steven S. Plotkin

The contribution to an organism's phenotype from one genetic locus may depend upon the status of other loci. Such epistatic interactions among loci are now recognized as fundamental to shaping the process of adaptation in evolving…

Populations and Evolution · Quantitative Biology 2012-12-18 Jeremy A. Draghi , Joshua B. Plotkin

The motion involved in barrier crossing for protein folding are investigated in terms of the chain dynamics of the polymer backbone, completing the microscopic description of protein folding presented in the previous paper. Local reaction…

Soft Condensed Matter · Physics 2009-10-31 John J. Portman , Shoji Takada , Peter G. Wolynes

Structural biology has long been dominated by the one sequence, one structure, one function paradigm, yet many critical biological processes - from enzyme catalysis to membrane transport - depend on proteins that adopt multiple…

The folding kinetics of a number of sequences for off-lattice continuum model of proteins is studied using Langevin simulations at two values of the friction coefficient. We show that there is a remarkable correlation between folding times,…

Statistical Mechanics · Physics 2008-02-03 T. Veitshans , D. K. Klimov , D. Thirumalai

A molecular understanding of how protein function is related to protein structure will require an ability to understand large conformational changes between multiple states. Unfortunately these states are often separated by high free energy…

Biological Physics · Physics 2011-08-08 Juan R. Perilla , Thomas B. Woolf

Comprehensive knowledge of protein-ligand interactions should provide a useful basis for annotating protein functions, studying protein evolution, engineering enzymatic activity, and designing drugs. To investigate the diversity and…

Biomolecules · Quantitative Biology 2009-02-11 Akira R. Kinjo , Haruki Nakamura

The ability to absorb mutations while retaining structure and function, or mutational robustness, is a remarkable property of natural proteins. In this Letter, we use a computational model of organismic evolution [Zeldovich et al, PLOS Comp…

Biomolecules · Quantitative Biology 2008-06-25 Konstantin B. Zeldovich , Eugene I. Shakhnovich

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

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

We explored the Protein DataBank (PDB) to collect protein-ssDNA structures and create a multiconformational docking benchmark including both bound and unbound protein structures. Due to ssDNA high flexibility when not bound, no ssDNA…

Quantitative Methods · Quantitative Biology 2022-10-21 Dominique Mias-Lucquin , Isaure Chauvot de Beauchene

Proteins' fuzziness are features for communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene…

Quantitative Methods · Quantitative Biology 2024-07-25 Pengzhi Zhang , Jules Nde , Yossi Eliaz , Nathaniel Jennings , Piotr Cieplak , Margaret. S. Cheung

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

Quantitative Methods · Quantitative Biology 2012-07-12 Alan Lapedes , Bertrand Giraud , Christopher Jarzynski