Crystal structure-based virtual screening for fragment-like ligands of the human histamine H(1) receptor.

ABSTRACT: The recent crystal structure determinations of druggable class A G protein-coupled receptors (GPCRs) have opened up excellent opportunities in structure-based ligand discovery for this pharmaceutically important protein family. We have developed and validated a customized structure-based virtual fragment screening protocol against the recently determined human histamine H(1) receptor (H(1)R) crystal structure. The method combines molecular docking simulations with a protein-ligand interaction fingerprint (IFP) scoring method. The optimized in silico screening approach was successfully applied to identify a chemically diverse set of novel fragment-like (≤22 heavy atoms) H(1)R ligands with an exceptionally high hit rate of 73%. Of the 26 tested fragments, 19 compounds had affinities ranging

SUBMITTER: de Graaf C 

PROVIDER: S-EPMC3228891 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature