EFFECT OF GLY 16 ARG SINGLE NUCLEOTIDE POLYMORPHISM ON AGONIST BINDING TO BETA 2 ADRENERGIC RECEPTOR – A STRUCTURAL PHARMACOGENOMIC APPROACH

Asthma is obAdd Newstructive disease characterized by bronchoconstriction and inflammation for which beta 2 (β₂) agonists that act through the β₂ adrenoceptor are the first line agents of choice. Glycine16Arginine (Gly16Arg) is a common single nucleotide polymorphism (SNP) of β₂ adrenoceptor whose effects on treatment response remain inconclusive. Hence the study aims to understand and determine the effect of the Gly16Arg SNP on β₂-agonist binding and treatment responsiveness. Structure guided mutagenesis was performed with discovery studio tool, energy minimization was performed using Chemistry at Harvard Macromolecular Mechanics(CHARMM) force field, protein confirmation was studied using Ramachandran plot, Molecular docking analysis was performed using Autodock 4.2 and statistical analysis was performed using Graph pad prism 6.0. Statistically significant difference was observed between the binding energies of Glycine16 (Gly16) and Arginine16 (Arg16) groups. Further, the binding energies of β₂ agonists were found to be comparatively less in Arg16 group than the Gly16 group suggesting that the Arg16 variant carriers may be poor responders of β₂ – sympathomimetic therapy. Presence of functional non synonymous single nucleotide polymorphisms in the β₂ adrenoceptor significantly alters β₂sympathomimetic binding. Patients with Arg16 variant may therefore be poor or non-responders of conventional bronchodilator therapy