Boosting the conformational sampling by combining replica exchange with solute tempering and well‐sliced metadynamics

Replica Exchange Molecular Dynamics (REMD) is a widely used enhanced sampling method for accelerating biomolecular simulations. During the past two decades, several variants of REMD have been developed to further improve the rate of conformational sampling of REMD. One such variant, Reservoir REMD (RREMD), was shown to improve the rate of conformational sampling by around 5-20x. Despite the significant increase in sampling speed, RREMD methods have not been widely used due to the difficulties in building the reservoir and also due to the code not being available on the GPUs.<br><br>In this work, we ported the AMBER RREMD code onto GPUs making it 20x faster than the CPU code. Then, we explored protocols for building Boltzmann-weighted reservoirs as well as non-Boltzmann reservoirs, and tested how each choice affects the accuracy of the resulting RREMD simulations. We show that, using the recommended protocols outlined here, RREMD simulations can accurately reproduce Boltzmann-weighted ensembles obtained by much more expensive conventional REMD simulations, with at least 15x faster convergence rates even for larger proteins (>50 amino acids) compared to conventional REMD.

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Conformational sampling of metastable states: Tq-REM as a novel replica exchange method

Physical Chemistry Chemical Physics ◽

10.1039/c6cp05322j ◽

2017 ◽

Vol 19 (7) ◽

pp. 5454-5464 ◽

Cited By ~ 2

Author(s):

MinJun Lee ◽

Jeseong Yoon ◽

Soonmin Jang ◽

Seokmin Shin

Keyword(s):

Metastable States ◽

Replica Exchange ◽

Conformational Sampling ◽

Sampling Efficiency ◽

Exchange Method ◽

Replica Exchange Method

We propose a new replica exchange scheme (Tq-REM) created by combining the conventional temperature-REM (T-REM) and one of the Hamiltonian-REMs (q-REM), which shows improved sampling efficiency of metastable states.

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Enhanced conformational sampling of carbohydrates by Hamiltonian replica-exchange simulation

Glycobiology ◽

10.1093/glycob/cwt093 ◽

2013 ◽

Vol 24 (1) ◽

pp. 70-84 ◽

Cited By ~ 22

Author(s):

Sushil Kumar Mishra ◽

Mahmut Kara ◽

Martin Zacharias ◽

Jaroslav Koča

Keyword(s):

Replica Exchange ◽

Conformational Sampling ◽

Hamiltonian Replica Exchange

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Multiscale implementation of infinite-swap replica exchange molecular dynamics

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1605089113 ◽

2016 ◽

Vol 113 (42) ◽

pp. 11744-11749 ◽

Cited By ~ 14

Author(s):

Tang-Qing Yu ◽

Jianfeng Lu ◽

Cameron F. Abrams ◽

Eric Vanden-Eijnden

Keyword(s):

Molecular Dynamics ◽

Joint Distribution ◽

Jump Process ◽

Stochastic Simulation Algorithm ◽

Replica Exchange ◽

Conformational Sampling ◽

Markov Jump ◽

Replica Exchange Molecular Dynamics ◽

Different Temperatures ◽

Heterogeneous Multiscale

Replica exchange molecular dynamics (REMD) is a popular method to accelerate conformational sampling of complex molecular systems. The idea is to run several replicas of the system in parallel at different temperatures that are swapped periodically. These swaps are typically attempted every few MD steps and accepted or rejected according to a Metropolis–Hastings criterion. This guarantees that the joint distribution of the composite system of replicas is the normalized sum of the symmetrized product of the canonical distributions of these replicas at the different temperatures. Here we propose a different implementation of REMD in which (i) the swaps obey a continuous-time Markov jump process implemented via Gillespie’s stochastic simulation algorithm (SSA), which also samples exactly the aforementioned joint distribution and has the advantage of being rejection free, and (ii) this REMD-SSA is combined with the heterogeneous multiscale method to accelerate the rate of the swaps and reach the so-called infinite-swap limit that is known to optimize sampling efficiency. The method is easy to implement and can be trivially parallelized. Here we illustrate its accuracy and efficiency on the examples of alanine dipeptide in vacuum and C-terminal β-hairpin of protein G in explicit solvent. In this latter example, our results indicate that the landscape of the protein is a triple funnel with two folded structures and one misfolded structure that are stabilized by H-bonds.

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