In silico Modeling of α1A-Adrenoceptor: Interaction of its Normal and Mutated Active Sites with Noradrenaline as well as its Agonist and Antagonist
Ramchandran Vijayan, Naidu Subbarao and Birendra Nath Mallick
DOI : 10.3844/ajbbsp.2007.216.224
American Journal of Biochemistry and Biotechnology
Volume 3, Issue 4
Noradrenaline, like most other neurotransmitters, acts through various adrenoceptor subtypes. The structure and active site of adrenoceptors for the binding of noradrenaline were unknown, however, such information are crucial for understanding the molecular mechanism of action of neurotransmitters, including noradrenaline, in health and disease as well as for drug designing. In this in silico study, we modeled the Î±1A-adrenoceptor; a G protein coupled receptor and defined its active site. Further, molecular docking and interaction of noradrenaline and its agonist as well as antagonist with the so defined active site of the receptor was studied before and after in silico site directed mutation of several amino acid residues forming the active site. Our results indicate that the ARG166 is the most crucial residue for binding of noradrenaline and methoxamine to Î±1A-adrenoceptor and ILE178 is the most important residue for binding of prazosin to it. Thus, the observations provide new insights into the structure function relationship of Î±1A-adrenoceptor. A significant finding of this study is that the same residue of the active site may not be necessary for binding of a receptor with its natural ligand and its pharmacologically active known agonist and antagonist.
© 2007 Ramchandran Vijayan, Naidu Subbarao and Birendra Nath Mallick. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.