Boosting the conformational sampling by combining replica exchange with solute tempering and well‐sliced metadynamics. Issue 31 (29th September 2021)

• Record Type: Journal Article
• Authors: Kapakayala, Anji Babu; Nair, Nisanth N.
• Is Part Of: Journal of computational chemistry. Volume 42:Issue 31(2021)
• Page Start: 2233
• Page End: 2240
• Publication Date: 2021-09-29
• Subjects: free energy calculations -- Hamiltonian replica exchange -- metadynamics -- molecular dynamics -- REMD -- replica exchange molecular dynamics -- REST2 -- umbrella sampling -- weighted histogram analysis; Chemistry -- Data processing -- Periodicals; 542.85
• DOI: 10.1002/jcc.26752
• Languages: English
• ISSNs: 0192-8651

Abstract

Abstract: Methods that combine collective variable (CV) based enhanced sampling and global tempering approaches are used in speeding‐up the conformational sampling and free energy calculation of large and soft systems with a plethora of energy minima. In this paper, a new method of this kind is proposed in which the well‐sliced metadynamics approach (WSMTD) is united with replica exchange with solute tempering (REST2) method. WSMTD employs a divide‐and‐conquer strategy wherein high‐dimensional slices of a free energy surface are independently sampled and combined. The method enables one to accomplish a controlled exploration of the CV‐space with a restraining bias as in umbrella sampling, and enhance‐sampling of one or more orthogonal CVs using a metadynamics like bias. The new hybrid method proposed here enables boosting the sampling of more slow degrees of freedom in WSMTD simulations, without the need to specify associated CVs, through a replica exchange scheme within the framework of REST2. The high‐dimensional slices of the probability distributions of CVs computed from the united WSMTD and REST2 simulations are subsequently combined using the weighted histogram analysis method to obtain the free energy surface. We show that the new method proposed here is accurate, improves the conformational sampling, and achieves quick convergence in free energy estimates. We demonstrate this by computing the conformational free energy landscapes of solvated alanine tripeptide and Trp‐cage mini protein in explicit water. Abstract : A new method is proposed for efficient sampling of conformational space of large soft matter systems. The method permits one to drive a conformational change along a collective variable (CV) in a controlled fashion and exhaustive sampling of orthogonal coordinates through accelerating global motions (without specifying any CVs) and biased sampling of a priori chosen CVs. The method is shown to be very accurate and quite efficient for problems such as protein folding.