In silico approach to identify non-synonymous SNPs in human obesity related gene, MC3R (melanocortin-3-receptor)

Rajan Kumar Singh; Kulandaivelu Mahalingam

doi:10.1016/j.compbiolchem.2016.12.009

In silico approach to identify non-synonymous SNPs in human obesity related gene, MC3R (melanocortin-3-receptor)

Comput Biol Chem. 2017 Apr:67:122-130. doi: 10.1016/j.compbiolchem.2016.12.009. Epub 2016 Dec 29.

Authors

Rajan Kumar Singh¹, Kulandaivelu Mahalingam²

Affiliations

¹ Department of Bio-Medical Sciences, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamilnadu, India.
² Department of Bio-Medical Sciences, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamilnadu, India. Electronic address: kmahalingam@vit.ac.in.

PMID: 28073065
DOI: 10.1016/j.compbiolchem.2016.12.009

Abstract

The melanocortin-3-receptor (MC3R) is a novel gene candidate for human obesity, which involved in controlling the energy homeostasis and food intake behavior. The main aim behind this work is to investigate the potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in obesity related gene MC3R by using six computational tools viz., PolyPhen, I-Mutant, PROVEAN, SIFT, PANTHER and PhD-SNP. In our study, we predicted eight nsSNPs i.e., rs74315393 (Ile146Asn), rs368205448 (Asp121Tyr), rs143321797 (Phe45Ser), rs17847261 (Cys274Ser), rs144166442 (Pro257His), rs370533946 (Leu224Pro), rs371354428 (Pro72Leu) and rs373708098 (Gly249Ser) found to be potentially deleterious. The functional impact of three nsSNPs i.e., rs74315393, rs368205448 and rs143321797 have already been validated experimentally in the context of human obesity. Moreover, Homology modeling and structural analysis were carried out for already experimentally validated nsSNPs i.e., rs74315393, rs368205448 and rs143321797 to check the stability of predicted models. The mutant models showed higher energy and RMSD (Root mean square deviation) values. In addition, FTSite server predicted one nsSNP i.e., rs368205448 (Asp121Tyr) out of eight identified nsSNPs found in the MC3R protein binding site. Thus, the present computational study may suggest that predicted nsSNPs possibly be a better drug target and contribute to the treatment and better understanding of human obesity.

Keywords: Energy homeostasis; Homology modeling; MC3R; Obesity; SNPs.

MeSH terms

Binding Sites / genetics
Computer Simulation*
Humans
Ligands
Models, Chemical
Models, Molecular
Mutation
Polymorphism, Single Nucleotide / genetics*
Receptor, Melanocortin, Type 3 / genetics*
Sequence Homology, Nucleic Acid

Substances

Ligands
MC3R protein, human
Receptor, Melanocortin, Type 3