title: In silico binding characteristics between human histamine H1 receptor and antagonists.
abstract: It is widely acknowledged that the H(1) receptor antagonists have important therapeutic significance in the treatment of various allergic disorders, but little was known about the binding mode between the receptor and antagonists since the crystal structure of G-protein coupling receptors (GPCRs) were hard to obtain. In this paper, a theoretical three-dimensional model of human histamine H(1) receptor (HHR1) was developed on the basis of recently reported high resolution structures of human A(2A) adenosine receptor, human beta(2)-adrenoceptor and turkey beta(1)-adrenoceptor. Furthermore, three representative H(1) receptor antagonists were chosen for docking studies. Subsequently, a qualitative pharmacophore model was developed by Hiphop algorithm based on the docking conformations of these three antagonists. In this paper, active environment, certain key residues, and the corresponding pharmacophore features of H(1) receptor were identified by such combinations of receptor-based and ligand-based approaches, which would give sufficient guidance for the rational design of novel antihistamine agents.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Dali
authors.initials: D
authors.lastname: Yin
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D006634:Histamine H1 Antagonists / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D011969:Receptors, Histamine H1 / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013997:Time Factors
chemical_list: D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1