Banushkina, PV and Krivov, SV (2013) High-Resolution Free-Energy Landscape Analysis of α-Helical Protein Folding: HP35 and Its Double Mutant. Journal of Chemical Theory and Computation, 9 (12). 5257 - 5266. ISSN 1549-9618
Abstract
The free-energy landscape can provide a quantitative description of folding dynamics, if determined as a function of an optimally chosen reaction coordinate. Here, we construct the optimal coordinate and the associated free-energy profile for all-helical proteins HP35 and its norleucine (Nle/Nle) double mutant, based on realistic equilibrium folding simulations [Piana et al. Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 17845]. From the obtained profiles, we directly determine such basic properties of folding dynamics as the configurations of the minima and transition states (TS), the formation of secondary structure and hydrophobic core during the folding process, the value of the pre-exponential factor and its relation to the transition path times, the relation between the autocorrelation times in TS and minima. We also present an investigation of the accuracy of the pre-exponential factor estimation based on the transition-path times. Four different estimations of the pre-exponential factor for both proteins give k 0 (-1) values of approximately a few tens of nanoseconds. Our analysis gives detailed information about folding of the proteins and can serve as a rigorous common language for extensive comparison between experiment and simulation.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | (c) 2013, American Chemical Society. Reproduced in accordance with the publisher's self-archiving policy. |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Feb 2014 12:32 |
Last Modified: | 28 Mar 2018 21:40 |
Published Version: | http://dx.doi.org/10.1021/ct400651z |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/ct400651z |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:77839 |