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Identification of Novel Histamine H4 Ligands by Virtual Screening on Molecular Dynamics Ensembles
Author(s) -
Kiss Róbert,
Jójárt Balázs,
Schmidt Éva,
Kiss Béla,
Keserű György M.
Publication year - 2014
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201300072
Subject(s) - virtual screening , molecular dynamics , homology modeling , conformational isomerism , computational biology , docking (animal) , chemistry , histamine receptor , molecular model , ligand (biochemistry) , histamine h4 receptor , computer science , biological system , computational chemistry , stereochemistry , receptor , biology , molecule , biochemistry , medicine , histamine h2 receptor , nursing , antagonist , enzyme , organic chemistry
We report the identification of novel histamine H4 receptor ligands by ensemble docking on homology model conformers derived from molecular dynamics simulations. Selected receptor models from the trajectories demonstrated superior virtual screening performance compared to the initial models. The ensemble of the best models was able to retrieve a diverse set of known H4 ligands. Prospective virtual screening against these models and subsequent in vitro experimental validation identified novel H4 ligands. Compound 3 showing highest affinity and ligand efficiency represents an interesting scaffold for further medicinal chemistry exploration.