How Main-chains of Proteins Explore the Free-energy Landscape in Native States

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Dec 18

PMID 19073932

Citations 23

Authors

Patrick Senet

Gia G Maisuradze

Colette Foulie

Patrice Delarue

Harold A Scheraga

Affiliations

Soon will be listed here.

Abstract

Understanding how a single native protein diffuses on its free-energy landscape is essential to understand protein kinetics and function. The dynamics of a protein is complex, with multiple relaxation times reflecting a hierarchical free-energy landscape. Using all-atom molecular dynamics simulations of an alpha/beta protein (crambin) and a beta-sheet polypeptide (BS2) in their "native" states, we demonstrate that the mean-square displacement of dihedral angles, defined by 4 successive C(alpha) atoms, increases as a power law of time, t(alpha), with an exponent alpha between 0.08 and 0.39 (alpha = 1 corresponds to Brownian diffusion), at 300 K. Residues with low exponents are located mainly in well-defined secondary elements and adopt 1 conformational substate. Residues with high exponents are found in loops/turns and chain ends and exist in multiple conformational substates, i.e., they move on multiple-minima free-energy profiles.

Citing Articles

Einstein Model of a Graph to Characterize Protein Folded/Unfolded States.

Tyler S, Laforge C, Guzzo A, Nicolai A, Maisuradze G, Senet P Molecules. 2023; 28(18).

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Phosphorylation Induces Conformational Rigidity at the C-Terminal Domain of AMPA Receptors.

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