Multidimensional virtual‐system coupled canonical molecular dynamics to compute free‐energy landscapes of peptide multimer assembly

• Published in: Journal of computational chemistry 2019-10, Vol.40 (28), p.2453-2463
• Main Authors: Hayami, Tomonori, Higo, Junichi, Nakamura, Haruki, Kasahara, Kota
• Format: Article
• Language: English
• Subjects: Adaptive sampling; Alanine; Computer simulation; Coupling (molecular); enhanced conformational sampling; free‐energy landscape; generalized‐ensemble approach; Molecular dynamics; Peptides; protein–protein interaction; Sampling; Sampling methods
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.26020

An enhanced‐sampling method termed multidimensional virtual‐system coupled canonical molecular dynamics (mD‐VcMD) method is developed. In many cases, generalized‐ensemble methods realizing enhanced sampling, for example, adaptive umbrella sampling, apply an effective potential, which is derived from temporarily assumed canonical distribution as a function of one or more arbitrarily defined reaction coordinates. However, it is not straightforward to estimate the appropriate canonical distribution, especially for cases applying multiple reaction coordinates. The current method, mD‐VcMD, does not rely on the form of the canonical distribution. Therefore, it is practically useful to explore a high‐dimensional reaction‐coordinate space. In this article, formulation of mD‐VcMD and its evaluation with the simple molecular models consisting of three or four alanine peptides are presented. We confirmed that mD‐VcMD efficiently searched 2D and 3D reaction‐coordinate spaces defined as interpeptide distances. Direct comparisons with results of long‐term canonical MD simulations revealed that mD‐VcMD produces correct canonical ensembles. © 2019 Wiley Periodicals, Inc. A new sampling method for molecular dynamics (MD) simulations, multidimensional virtual‐system coupled canonical MD, is presented. In this method, the molecular system is coupled with the virtual system. Interactions between these systems enhance the conformational sampling. The method was examined using molecular systems that consists of trimer and tetramer of alanine peptides, and confirmed that the resultant ensembles agree with the ensembles generated by the long‐term conventional MD method.