PaCS-Toolkit: Optimized Software Utilities for Parallel Cascade Selection Molecular Dynamics (PaCS-MD) Simulations and Subsequent Analyses

Abstract

Parallel cascade selection molecular dynamics (PaCS-MD) is an enhanced conformational sampling method conducted as a "repetition of time leaps in parallel worlds", comprising cycles of multiple molecular dynamics (MD) simulations performed in parallel and selection of the initial structures of MDs for the next cycle. We developed PaCS-Toolkit, an optimized software utility enabling the use of different MD software and trajectory analysis tools to facilitate the execution of the PaCS-MD simulation and analyze the obtained trajectories, including the preparation for the subsequent construction of the Markov state model. PaCS-Toolkit is coded with Python, is compatible with various computing environments, and allows for easy customization by editing the configuration file and specifying the MD software and analysis tools to be used. We present the software design of PaCS-Toolkit and demonstrate applications of PaCS-MD variations: original targeted PaCS-MD to peptide folding; rmsdPaCS-MD to protein domain motion; and dissociation PaCS-MD to ligand dissociation from adenosine A 2A receptor.