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

Article English OPEN
Jensen, Christian H. ; Nerukh, Dmitry ; Glen, Robert C. (2008)
  • Subject:
    arxiv: Quantitative Biology::Biomolecules

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.
  • References (16)
    16 references, page 1 of 2

    [1] Y. Sugita and Y. Okamoto. Replica-exchange molecular dynamics method for protein folding. Chemical Physics Letters, 314(1-2):141{151, 1999.

    [2] X. Periole and A. E. Mark. Convergence and sampling e±ciency in replica exchange simulations of peptide folding in explicit solvent. Journal of Chemical Physics, 126(1):11, 2007.

    [3] A. Baumketner and J. E. Shea. The thermodynamics of folding of a beta hairpin peptide probed through replica exchange molecular dynamics simulations. Theoretical Chemistry Accounts, 116(1-3):262{273, 2006.

    [4] K. P. Ravindranathan, E. Gallicchio, R. A. Friesner, A. E. McDermott, and R. M. Levy. Conformational equilibrium of cytochrome p450bm-3 complexed with n-palmitoylglycine: A replica exchange molecular dynamics study. Journal of the American Chemical Society, 128(17):5786{5791, 2006.

    [5] D. Hamelberg, J. Mongan, and J. A. McCammon. Accelerated molecular dynamics: A promising and e±cient simulation method for biomolecules. Journal of Chemical Physics, 120(24):11919{11929, 2004.

    [6] A. F. Voter. Hyperdynamics: Accelerated molecular dynamics of infrequent events. Physical Review Letters, 78(20):3908{3911, 1997.

    [7] A. F. Voter. A method for accelerating the molecular dynamics simulation of infrequent events. Journal of Chemical Physics, 106(11):4665{4677, 1997.

    [8] N. Singhal, C. D. Snow, and V. S. Pande. Using path sampling to build better markovian state models: Predicting the folding rate and mechanism of a tryptophan zipper beta hairpin. Journal of Chemical Physics, 121(1):415{425, 2004.

    [9] G. Jayachandran, V. Vishal, and V. S. Pande. Using massively parallel simulation and markovian models to study protein folding: Examining the dynamics of the villin headpiece. Journal of Chemical Physics, 124(16), 2006.

    [10] W. C. Swope, J. W. Pitera, and F. Suits. Describing protein folding kinetics by molecular dynamics simulations. 1. theory. Journal of Physical Chemistry B, 108(21):6571{6581, 2004.

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