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Title: Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

Journal Article · · Journal of Chemical Physics
DOI:https://doi.org/10.1063/1.4946793· OSTI ID:22660837
;  [1];  [2]
  1. Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)
  2. Department of Chemistry, Division of Biomedical Engineering, Center of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)

Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

OSTI ID:
22660837
Journal Information:
Journal of Chemical Physics, Vol. 144, Issue 15; Other Information: (c) 2016 Author(s); Country of input: International Atomic Energy Agency (IAEA); ISSN 0021-9606
Country of Publication:
United States
Language:
English