An explicit-solvent conformation search method using open software

Abstract

Computer modeling is a popular tool to identify the most-probable conformers of a molecule. Although the solvent can have a large effect on the stability of a conformation, many popular conformational search methods are only capable of describing molecules in the gas phase or with an implicit solvent model. We have developed a work-flow for performing a conformation search on explicitly-solvated molecules using open source software. This method uses replica exchange molecular dynamics (REMD) to sample the conformational states of the molecule efficiently. Cluster analysis is used to identify themost probable conformations fromthe simulated trajectory. Thiswork-flowwas tested on drugmolecules α-amanitin and cabergoline to illustrate its capabilities and effectiveness. The preferred conformations of these molecules in gas phase, implicit solvent, and explicit solvent are significantly different.