An explicit-solvent conformation search method using open software

Kari Gaalswyk; Christopher N Rowley

doi:10.7717/peerj.2088

An explicit-solvent conformation search method using open software

PeerJ. 2016 May 31:4:e2088. doi: 10.7717/peerj.2088. eCollection 2016.

Authors

Kari Gaalswyk¹, Christopher N Rowley¹

Affiliation

¹ Department of Chemistry, Memorial University of Newfoundland , St. John's, Newfoundland and Labrador , Canada.

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 the most probable conformations from the simulated trajectory. This work-flow was tested on drug molecules 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.

Keywords: Cluster analysis; Conformation search; Explicit solvent; Replica exchange molecular dynamics.

Grants and funding

The authors received funding from the NSERC of Canada through the Discovery Grant program (Application 418505-2012). Kari Gaalswyk received funding from Memorial University. Computational resources were provided by Compute Canada (RAPI: djk-615-ab) through the Calcul Quebec and ACEnet consortia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.