title: Combining quantum mechanical ligand conformation analysis and protein modeling to elucidate GPCR-ligand binding modes.
abstract: SAR beyond protein-ligand interactions: By combining structure-affinity relationships, protein-ligand modeling studies, and quantum mechanical calculations, we show that ligand conformational energies and basicity play critical roles in ligand binding to the histamine H4 receptor, a GPCR that plays a key role in inflammation.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer-Gasse 5-11, 1121 Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schultes
authors.forename: Harald
authors.initials: H
authors.lastname: Engelhardt
authors.forename: Luc
authors.initials: L
authors.lastname: Roumen
authors.forename: Obbe P
authors.initials: OP
authors.lastname: Zuiderveld
authors.forename: Eric E J
authors.initials: EE
authors.lastname: Haaksma
authors.forename: Iwan J P
authors.initials: IJ
authors.lastname: de Esch
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
authors.forename: Chris
authors.initials: C
authors.lastname: de Graaf
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D011968:Receptors, Histamine / Q000737:chemistry / Q000378:metabolism*; D000074040:Receptors, Histamine H4
chemical_list: C418607:HRH4 protein, human; D008024:Ligands; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C012180:2-aminopyrimidine