Publication： Nature Scientific Reports

Date of Publication: 10 July 2018

Authors： Sang Won Jung, Minsup Kim, Steven Ramsey, Tom Kurtzman & Art E. Cho

DOI:10.1038/s41598-018-28546-z

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.