Homology Modeling of Human α~2A~-Adrenoceptor
Author(s) -
Jignesh Patel,
G Gourja,
Vivek Kumar,
Yogesh B. Narkhede,
Shikhar Gupta,
C. Gopi Mohan
Publication year - 2009
Publication title -
nature precedings
Language(s) - English
Resource type - Journals
ISSN - 1756-0357
DOI - 10.1038/npre.2009.4106.1
Subject(s) - homology modeling , g protein coupled receptor , homology (biology) , computational biology , receptor , protein data bank (rcsb pdb) , superfamily , sequence homology , bioinformatics , chemistry , biology , biochemistry , peptide sequence , amino acid , gene , enzyme
α~2A~-adrenoceptor (ADA2A) is a membrane bound receptor which has been classified as the member of larger superfamily G-protein coupled receptors (GPCRs); also known as seven transmembrane (7-TM) domains receptor. Around 50% drugs currently available in the market exert their effects through GPCRs. Membrane proteins are difficult to crystallize as compared to soluble proteins. There is a need of 3D-structure of ADA2A to understand binding modes of various agonists and antagonists and hence homology model of ADA2A was developed. Homology model of ADA2A constructed based on crystal structure of β~2~-adrenoceptor. The crystal structure of β~2~-adrenoceptor (PDB ID: 2RH1) was used as template, which has good sequence identity and higher resolution (2.4 Å) and models were generated using MODELLER9v7, among them some models were selected based on molpdf and DOPE score. The built homology model was evaluated using various programs like ERRAT, PROCHECK, PROSA2003, and WHAT_IF. The built homology model can be useful for designing more potent subtype selective antagonists or/and agonists and can provide guidance for mutagenesis studies
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