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

J. Chem. Phys. 129, 225102 (2008); doi:10.1063/1.3025888

Published 11 December 2008

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Christian H. Jensen, Dmitry Nerukh, and Robert C. Glen
Department of Chemistry, Unilever Centre for Molecular Science Informatics, University of Cambridge, Cambridge CB2 1EW, United Kingdom
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 1µs. 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. ©2008 American Institute of Physics
History: Received 9 August 2008; accepted 14 October 2008; published 11 December 2008
Permalink: http://link.aip.org/link/?JCPSA6/129/225102/1
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KEYWORDS and PACS

Keywords
PACS
  • 87.15.Cc
    Folding of biomolecules: thermodynamics, statistical mechanics, models and pathways
  • 87.15.hm
    Folding dynamics of biomolecules
  • 87.15.ap
    Molecular dynamics simulation in molecular biophysics
  • 87.10.Tf
    Molecular dynamics simulation (biological/medical physics)
  • 02.50.Ga
    Markov processes
  • YEAR: 2008

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PUBLICATION DATA

ISSN:
0021-9606 (print)   1089-7690 (online)
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