Homology Modeling of Human 5-HT2a Serotonin Receptor

摘要

We have developed a homology model of the human serotonin 5-HT2a receptor, a G protein-coupled receptor, based on the high-resolution crystal structure of the human beta-2 adrenergic receptor (2RH1). The homology model was built using the Biopolymer module in SYBYL, minimized with CHARMM, and subjected to validation with PROCHECK. A set of ligands comprising agonists and antagonists (both endogenous ligands and marketed drugs) were blind docked into the receptor using AutoDock 4.2, and all ligands were found to dock into the orthosteric binding site. The ligand-receptor binding interactions on the orthosteric binding sites were then investigated. The binding modes were compared with the site-directed mutagenesis data and a good correlation with the experimental data was observed. Therefore, we concluded that this model can be used for future drug design and discovery studies.