Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

Abstract

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways. © 2013 AIP Publishing LLC.

Efficient conformational sampling of proteins based on a multi-dimensional TaBoo SeArch algorithm: An application to folding of chignolin in explicit solvent

“…where the weights, w i , are determined so as to minimize the statistical error (see [1][2][3][4][5][6]9] for details). Finally, the FEL projected onto RCs, , is defined by the logarithmic form:…”

“…For another verification of the conformational sampling, the trajectories of TBSA were projected onto a sub-space spanned by the pre-defined RC in Refs [2,4,30], the characteristic hydrogen bonding distances in the backbone (HB1 and HB2). Figure 5a-d shows the projections of the trajectories onto the sub-spaced in the 1st, 10th, 20th, 30th, 40th, 50th, and 100th cycles, respectively.…”

“…Recently, we have proposed a series of methodologies to sample the rare events efficiently, referred to as Parallel CaScade Molecular dynamics (PaCS-MD) [4], Fluctuation Flooding Method (FFM) [6], Outlier FLOODing (OFLOOD) method [7], and TaBoo SeArch (TBSA) algorithm [9] (See Ref. [8] for details).…”

“…These problems still remain as crucial issues to be addressed for sampling the rare events. For these reasons, several enhanced conformational sampling methods have so far been developed to effectively sample the rare events [1][2][3][4][5][6][7][8][9].…”

Multiscale enhanced sampling driven by multiple coarse-grained models

“…This system has been frequently used for validation of the enhanced sampling methods [8,[13][14][15][16][17][18]. In our previous paper [8], the scalability of the MSES was shown to be better than the temperature replica exchange study [13].…”