Parallel continuous simulated tempering and its applications in large-scale molecular simulations

Abstract

In this paper, we introduce a parallel continuous simulated tempering (PCST) method for enhanced sampling in studying large complex systems. It mainly inherits the continuous simulated tempering (CST) method in our previous studies [C. Zhang and J. Ma, J. Chem. Phys. 130, 194112 (2009); 132, 244101 (2010)], while adopts the spirit of parallel tempering (PT), or replica exchange method, by employing multiple copies with different temperature distributions. Differing from conventional PT methods, despite the large stride of total temperature range, the PCST method requires very few copies of simulations, typically 2-3 copies, yet it is still capable of maintaining a high rate of exchange between neighboring copies. Furthermore, in PCST method, the size of the system does not dramatically affect the number of copy needed because the exchange rate is independent of total potential energy, thus providing an enormous advantage over conventional PT methods in studying very large systems. The sampling efficiency of PCST was tested in two-dimensional Ising model, LennardJones liquid and all-atom folding simulation of a small globular protein trp-cage in explicit solvent. The results demonstrate that the PCST method significantly improves sampling efficiency compared with other methods and it is particularly effective in simulating systems with long relaxation time or correlation time. We expect the PCST method to be a good alternative to parallel tempering methods in simulating large systems such as phase transition and dynamics of macromolecules in explicit solvent.

Refining protein structures using enhanced sampling techniques with restraints derived from an ensemble‐based model

“…The PCST‐EBM method described in this paper is a direct extension of our previous PCST‐SBM method . It combined an enhanced sampling method, parallel continuous simulated tempering (PCST), with a temperature‐dependent coordinate‐based restraint, the ensemble‐based model (EBM), to conduct thorough search of configurational space in the process of protein structural refinement. The EBM restraint was constructed in such a way that the non‐bonded Lennard–Jones term for each contacting atomic pair, in single‐reference‐based SBM potential used in previous paper, was replaced by a multi‐Gaussian function for including the contributions of partial structural “correctness” distributed among an ensemble of predicted structures.…”

“…We apply PCST simulation method in this work . It uses generalized ensemble, which changes the traditional Boltzmann distribution to other mathematical forms W ( X , β ).…”

“…We can treat the probability distribution as the sum of Boltzmann distributions at different temperatures with a polynomial‐like weight function β − γ as well as a Gaussian‐like weight function with the mean value of and width of σ i . More details can be found in PCST paper …”

“…In our previous paper, in order to improve the low‐accuracy protein structural models, the parallel continuous simulated tempering (PCST) was combined with a temperature‐dependent restraint using structure‐based model (SBM) . In fully solvated molecular dynamics simulation for refinement, it was shown that PCST‐SBM method was able to achieve a more thorough sampling in the configurational space.…”

PAGE4 and Conformational Switching: Insights from Molecular Dynamics Simulations and Implications for Prostate Cancer

“…The segmentation scheme is shown in Figure 1. Segments are simulated with an enhanced sampling method CST (Continuous Simulated Tempering) [27,52] to achieve an equilibrated structural ensemble. The CST was performed in a temperature range of 293-350K and the structures that were sampled at temperatures below 330K were selected for a structural clustering.…”