We present a new statistical model of unfolded proteins in which the stiffness of polypeptide backbone is taken into account.
We construct and solve a mean field equation which has the form of a diffusion equation and derive the distribution function
for conformations of unfolded polypeptides. Accounting for the stiffness of the protein backbone results in a more accurate
description of general properties of a polypeptide chain, such as its gyration radius. We then use the distribution function
of a semistiff protein within a previously developed theoretical framework [J. Biomol. NMR 39, 1 (2007)] to determine the nuclear magnetic resonance (NMR) residual dipolar couplings (RDCs) in unfolded proteins. The
calculated RDC profiles (dependence of the RDC value on the residue number) exhibit a more prominent bell-like shape and a
better agreement with experimental data as compared to the previous results obtained with the random flights chain model.
[Show abstract][Hide abstract] ABSTRACT: We present a novel statistical mechanics formalism for the theoretical description of the process of protein folding$\leftrightarrow$unfolding transition in water environment. The formalism is based on the construction of the partition function of a protein obeying two-stage-like folding kinetics. Using the statistical mechanics model of solvation of hydrophobic hydrocarbons we obtain the partition function of infinitely diluted solution of proteins in water environment. The calculated dependencies of the protein heat capacities upon temperature are compared with the corresponding results of experimental measurements for staphylococcal nuclease and metmyoglobin. Comment: 24 pages, 3 figures
[Show abstract][Hide abstract] ABSTRACT: Proteins are biological polymers consisting of elementary structural units, amino acids. Being synthesized at ribosome, proteins are exposed to the cell interior, where they fold into their unique three dimensional structure. The correct folding of protein is of crucial importance for the protein’s proper functioning. The current state-of-the-art in experimental and theoretical studies of the protein folding process are described in recent reviews.
Theory of Phase Transitions in Polypeptides and Proteins, 01/2011: pages 101-118; , ISBN: 978-3-642-22591-8
[Show abstract][Hide abstract] ABSTRACT: Intrinsically disordered proteins (IDPs) have been shown to be involved in a number of cellular functions, in addition to their predominance in diseased states. α-synuclein may be described as one such IDP implicated in the pathology of Parkinson's disease. Understanding the conformational characteristics of the monomeric state of α-synuclein is necessary for understanding the role of the monomer conformation in aggregation. Polymer theories have been applied to investigate the statistical properties of homopolymeric IDPs. Here we use Replica Exchange Molecular Dynamics (REMD) simulations using temperature as a proxy for solvent quality to examine how well these theories developed for homopolymeric chains describe heteropolymeric α-synuclein. Our results indicate that α-synuclein behaves like a homopolymer at the extremes of solvent quality, while in the intermediate solvent regime, the uneven distribution of charged residues along the sequence strongly influences the conformations adopted by the chain. We refine the ensemble extracted from the REMD simulations of α-synuclein, which shows the best qualitative agreement with experiment, by fitting to the experimental NMR Residual Dipolar Couplings (RDCs) and Paramagnetic Relaxation Enhancements (PREs). Our results demonstrate that the detailed shape of the RDC patterns are sensitive to the angular correlations that are local in sequence while longer range anti-correlations which arise from packing constraints affect the RDC magnitudes.
Journal of Chemical Theory and Computation 10/2012; 8(10):3929-3942. DOI:10.1021/ct300241t · 5.50 Impact Factor
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