Kiss Róbert, Kovári Zoltán, Keseru György M
Department of Computer Assisted Drug Discovery, Gedeon Richter Ltd., H-1475, Budapest 10, P.O. Box 27, Hungary.
Eur J Med Chem. 2004 Nov;39(11):959-67. doi: 10.1016/j.ejmech.2004.07.009.
Three-dimensional model of the human histamine H1 receptor was developed by homology modelling using the high resolution structure of bovine rhodopsin as template. Genetic algorithm based docking calculations were used to identify the role of several amino acids having an effect on agonist or antagonist binding. Binding mode analyses of mepyramine, desloratidine, loratidine and acrivastine allowed us to rationalise their binding affinity. Binding site mapping resulted in seven new potential aromatic interaction points (Tyr 108, Phe 184, Phe 190, Phe 199, Phe 424, Trp 428, Tyr 431), that took part in forming the lipophilic pocket of the antagonist binding cavity.
利用牛视紫红质的高分辨率结构作为模板，通过同源建模构建了人组胺H1受体的三维模型。基于遗传算法的对接计算用于确定几个对激动剂或拮抗剂结合有影响的氨基酸的作用。对美吡拉敏、地氯雷他定、氯雷他定和阿伐斯汀的结合模式分析使我们能够合理化它们的结合亲和力。结合位点映射产生了七个新的潜在芳香相互作用点（酪氨酸108、苯丙氨酸184、苯丙氨酸190、苯丙氨酸199、苯丙氨酸424、色氨酸428、酪氨酸431），这些点参与形成拮抗剂结合腔的亲脂性口袋。
