Water Pharmacophore: Designing Ligands using Molecular Dynamics Simulations with Water.
Sci Rep
; 8(1): 10400, 2018 Jul 10.
Article
in En
| MEDLINE
| ID: mdl-29991756
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Conformation
/
Water
/
Molecular Dynamics Simulation
/
High-Throughput Screening Assays
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2018
Document type:
Article