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

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de Graaf C, Kooistra AJ, Vischer HF, Katritch V, Kuijer M, Shiroishi M, Iwata S, Shimamura T, Stevens RC, de Esch IJ, Leurs R

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

J Med Chem. 2011 Dec 8;54(23):8195-206. doi: 10.1021/jm2011589. Epub 2011 Nov 7.

PubMed ID

22007643 [ View in PubMed

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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 (

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Doxepin	Histamine H1 receptor	Ki (nM)	0.178	N/A	N/A	Details
Mepyramine	Histamine H1 receptor	Ki (nM)	2.09	N/A	N/A	Details