Anna V. Glyakina and Leonid B. Pereyaslavets contributed equally to this work.
Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure
Article first published online: 20 JUN 2013
Copyright © 2013 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 81, Issue 9, pages 1527–1541, September 2013
How to Cite
Glyakina, A. V., Pereyaslavets, L. B. and Galzitskaya, O. V. (2013), Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure. Proteins, 81: 1527–1541. doi: 10.1002/prot.24301
- Issue published online: 23 AUG 2013
- Article first published online: 20 JUN 2013
- Accepted manuscript online: 15 APR 2013 07:55AM EST
- Manuscript Accepted: 28 MAR 2013
- Manuscript Revised: 27 MAR 2013
- Manuscript Received: 13 NOV 2012
- Russian Foundation for Basic Research. Grant Number: 11-04-00763
- Russian Academy of Sciences (programs “Molecular and Cell Biology”). Grant Number: 01201353567
- Fundamental Sciences to Medicine
- protein folding;
- folding intermediates;
- folding nuclei;
- nucleation mechanism;
- diffusion-collision mechanism;
- right- and left-handed proteins
Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins.Proteins 2013; © 2013 Wiley Periodicals, Inc.