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

Qin Qiao, Hou-Dao Zhang, Xuhui Huang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.
Original languageEnglish (US)
Pages (from-to)154107
Issue number15
StatePublished - Apr 19 2016
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2022-06-01
Acknowledgements: We acknowledge the support from the National Basic Research Program of China (973 Program, No. 2013CB834703), the National Natural Science Foundation of China (No. 21273188), and the Hong Kong Research Grants Council (Nos. ECS 60981, 16304215, HKUST C6009-15G, and AoE/M-09/12). The computer resources are provided by KAUST Supercomputing Laboratory.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

ASJC Scopus subject areas

  • General Physics and Astronomy
  • Physical and Theoretical Chemistry


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