Insilico Prediction Of Functional And Structural Impact Of Novel Nonsynonymous Snps In Human Adrenergic Beta-Receptors

Research Article
Praveen P. Balgir., Rajesh Kumar Goel., Jaspreet Kaur.,Maleeka Sharma and Shobha R. Dhiman
DOI: 
xxx-xxxxx-xxxx
Subject: 
science
KeyWords: 
GPCRs; Adrenergic receptors; nsSNPs; Insilico; Prediction; Protein structure
Abstract: 

G-protein-coupled receptors (GPCRs) are the most common protein target among currently available marketed drugs. As a result, they were among the first group of proteins whose genetic variability was studied extensively. Beta-adrenergic receptors (ADRBs) are most widely studied GPCRs and most commonly used drugs are the β-adrenergic receptor blockers. Defects in phenotypes and functions are due to non-synonymous single nucleotide polymorphisms (nsSNPs), which are crucial to predict the genetic basis of diseases like asthma, hypertension, myocardial infarction and cardiovascular disease. Present study is an attempt, using different in silico tools, to predict all nsSNPs and the plausible effect of all these mutations on the structural and functional conformation of the protein. As per NCBI SNP Database, 39 nsSNPs of adrenoceptor beta 1 (ADRB1) and 43 of adrenoceptor beta 2 (ADRB2) are predicted in coding region of these genes. Out of these 9 nsSNPs of ADRB1 and 5 of ADRB2 lie in the functionally important sites like ligand binding, Phosphorylation, Glycosylation, Disulfide bond formation and Myristolyation. These variations were analyzed using SIFT, PolyPhen 2, MuPro, PANTHER, PROVEAN and MutPred. Thus, we hypothesized that these rare looked upon variations have the potential to result in change at phenotypic level and should be investigated by subsequent imperical approach to predict as no population data is available for many of these SNPs.