Open Access
Article
Two-state protein folding kinetics through all-atom molecular dynamics based sampling
Peter G Bolhuis1
1
van't Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018 WV Amsterdam, The Netherlands. bolhuis@science.uva.nl
DOI: 10.2741/3415 Volume 14 Issue 8, pp.2801-2828
Published: 01 January 2009
(This article belongs to the Special Issue Atomistic simulations in biosciences: models and methods)
Abstract

This review focuses on advanced computational techniques that employ all atom molecular dynamics to study the folding of small two state proteins. As protein folding is a rare event process, special sampling techniques are required to overcome high folding free energy barriers. Several biased sampling methods enable computation of the free energy landscape. Trajectory based sampling methods can assess the kinetics and the dynamical folding mechanisms. Proper sampling is only the first step, and further analysis is required to obtain the folding mechanisms reaction coordinate. Only a combination of several simulation techniques can solve the sampling problems connected with all-atom protein folding, and allow computation of experimental observables that can validate the force fields and simulation techniques. Several of the involved issues are illustrated with folding of small protein (fragments) such as beta hairpins and the Trp-cage mini protein.

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Peter G Bolhuis. Two-state protein folding kinetics through all-atom molecular dynamics based sampling. Frontiers in Bioscience-Landmark. 2009. 14(8); 2801-2828.