MuSTAR MD: Multi-scale sampling using temperature accelerated and replica exchange molecular dynamics

Abstract

A new and efficient conformational sampling method, MuSTAR MD (Multi-scale Sampling using Temperature Accelerated and Replica exchange Molecular Dynamics), is proposed to calculate the free energy landscape on a space spanned by a set of collective variables. This method is an extension of temperature accelerated molecular dynamics and can also be considered as a variation of replica-exchange umbrella sampling. In the MuSTAR MD, each replica contains an all-atom finegrained model, at least one coarse-grained model, and a model defined by the collective variables that interacts with the other models in the same replica through coupling energy terms. The coarsegrained model is introduced to drive efficient sampling of large conformational space and the finegrained model can serve to conduct more accurate conformational sampling. The collective variable model serves not only to mediate the coarse-and fine-grained models, but also to enhance sampling efficiency by temperature acceleration. We have applied this method to Ala-dipeptide and examined the sampling efficiency of MuSTAR MD in the free energy landscape calculation compared to that for replica exchange molecular dynamics, replica exchange umbrella sampling, temperature accelerated molecular dynamics, and conventional MD. The results clearly indicate the advantage of sampling a relatively high energy conformational space, which is not sufficiently sampled with other methods. This feature is important in the investigation of transition pathways that go across energy barriers. MuSTAR MD was also applied to Met-enkephalin as a test case in which two Gō-like models were employed as the coarse-grained model. © 2013 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.

Temperature-accelerated molecular dynamics gives insights into globular conformations sampled in the free state of the AC catalytic domain

“…TAMD can be used to reconstruct the free‐energy landscape from direct sampling via reweighting, or using a mean‐force interpolation method . TAMD and its extensions have already been applied to a variety of rare events sampling studies and have proved to be particularly useful in protein conformational searches …”

Extended Phase-Space Methods for Enhanced Sampling in Molecular Simulations: A Review

“…In particular, in the latter case, TAMD was used to enhance the flexible fitting of all-atom protein and RNA models into low-resolution density maps. In Yamamori and Kitao ( 2013 ), an interesting combination of TAMD and Replica Exchange Umbrella Sampling (REUS) was proposed. More recently, TAMD was combined with a soft-ratcheting algorithm to achieve a focused exploration of the CV space by relying on low-resolution or even qualitative experimental information (Cortes-Ciriano et al, 2015 ).…”

Energy Landscape of All-Atom Protein-Protein Interactions Revealed by Multiscale Enhanced Sampling

“…Our previous studies on the folding dynamics of chignolin [29] , [31] and on the ordering transition of an intrinsically disordered protein (sortase) [30] have demonstrated the outstanding capability of the all-atom conformational samplings of large proteins in explicit solvent. The use of multiscale scheme has also been aimed to develop the CG force fields from the MM simulations by bottom-up approach [32] – [34] , [38] , and applied for enhanced sampling such as resolution replica exchange [39] , [40] , adiabatic coupling [41] , [42] and temperature accelerated MD [43] – [46] .…”