Controlling protein molecular dynamics:how to accelerate folding while preserving the native state


The dynamics of peptides and proteins generated by classical molecular dynamics (MD) is described by using a Markov model. The model is built by clustering the trajectory into conformational states and estimating transition probabilities between the states. Assuming that it is possible to influence the dynamics of the system by varying simulation parameters, we show how to use the Markov model to determine the parameter values that preserve the folded state of the protein and at the same time, reduce the folding time in the simulation. We investigate this by applying the method to two systems. The first system is an imaginary peptide described by given transition probabilities with a total folding time of 1 micros. We find that only small changes in the transition probabilities are needed to accelerate (or decelerate) the folding. This implies that folding times for slowly folding peptides and proteins calculated using MD cannot be meaningfully compared to experimental results. The second system is a four residue peptide valine-proline-alanine-leucine in water. We control the dynamics of the transitions by varying the temperature and the atom masses. The simulation results show that it is possible to find the combinations of parameter values that accelerate the dynamics and at the same time preserve the native state of the peptide. A method for accelerating larger systems without performing simulations for the whole folding process is outlined.

Publication DOI:
Divisions: College of Engineering & Physical Sciences > Systems analytics research institute (SARI)
Additional Information: Copyright (2008) American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Jensen, CH, Nerukh, D & Glen, RC 2008, 'Controlling protein molecular dynamics: how to accelerate folding while preserving the native state', The journal of chemical physics , vol 129, no. 22 and may be found at
Uncontrolled Keywords: amino acid sequence,Markov chains,molecular models,oligopeptides,protein folding,proteins,temperature,time factors,Physical and Theoretical Chemistry,Medicine(all),Physics and Astronomy(all)
Publication ISSN: 1089-7690
Last Modified: 29 Feb 2024 08:09
Date Deposited: 11 Mar 2019 18:06
Full Text Link: http://jcp.aip. ... /i22/p225102_s1
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2008-12-14
Published Online Date: 2008-12-11
Authors: Jensen, Christian H.
Nerukh, Dmitry (ORCID Profile 0000-0001-9005-9919)
Glen, Robert C.



Version: Accepted Version

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