Watermelon: setup and validation of an in silico fragment-based approach.

ABSTRACT: We present a new computational approach, named Watermelon, designed for the development of pharmacophore models based on receptor structures. The methodology involves the sampling of potential hotspots for ligand interactions within a protein target's binding site, utilising molecular fragments as probes. By employing docking and molecular dynamics (MD) simulations, the most significant interactions formed by these probes within distinct regions of the binding site are identified. These interactions are subsequently transformed into pharmacophore features that delineates key anchoring sites for potential ligands. The reliability of the approach was experimentally validated using the monoacylglycerol lipase (MAGL) enzyme. The generated pharmacophore model captured features representi

SUBMITTER: Di Stefano M 

PROVIDER: S-EPMC11232643 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature