Water Pharmacophore: Designing Ligands using Molecular Dynamics Simulations with Water

Authors

Sang Won Jung, Korea University
Minsup Kim, Korea University
Steven Ramsey, CUNY Lehman CollegeFollow
Tom Kurtzman, CUNY Lehman CollegeFollow
Art E. Cho, Korea University

Document Type

Article

Publication Date

7-10-2018

Abstract

In this study, we demonstrate a method to construct a water-based pharmacophore model which can be utilized in the absence of known ligands. This method utilizes waters found in the binding pocket, sampled through molecular dynamics. Screening of compound databases against this water-based pharmacophore model reveals that this approach can successfully identify known binders to a target protein. The method was tested by enrichment studies of 7 therapeutically important targets and compared favourably to screening-by-docking with Glide. Our results suggest that even without experimentally known binders, pharmacophore models can be generated using molecular dynamics with waters and used for virtual screening.

Comments

This article was originally published in Scientific Reports, available at DOI:10.1038/s41598-018-28546-z.

This article is licensed under a Creative Commons Attribution 4.0 International License.