Computational Investigations on Structural and Functional Impact of SNP in Parkinson’s Disease Associated With Human Monoamine Oxidase-B (Mao-B)

17 Pages Posted: 30 Apr 2019

See all articles by Vishnu Sankar S.

Vishnu Sankar S.

Department of Chemistry,NSS Hindu College

Rohit S. Prasad

Department of Biotechnology,SCT college of Engineering

A. Ronaldo Anuf

Department of Biotechnology,Kamaraj College of Engineering and Technology

M. S. Latha

Department of Chemistry,Sree Narayana College

Date Written: April 11, 2019

Abstract

Single nucleotide polymorphism (SNP) is type of mutation and one of the major factor in determining susceptibility of an individual to a particular disease and response to the action of a drug. Thus mapping the structural and functional effects of SNP is the most important step in drug research and development in the context of personalized medicine. Parkinson’s disease is a neurodegenerative disorder affecting central nervous system (CNS) usually associated with aging. The symptoms of this disease includes nervous coordination problems like difficulty in walking, swallowing, chewing, slowness of movement and speaking along with other emotional problems like depression. The inhibition of metabolic enzyme monoamine oxidase B (MAO-B) is a key step to suppress the progression of the disease. The three dimensional crystal structure of the MAO-B was taken from Protein Data Bank (PDB ID: 4CRT). Gene name of the enzyme were selected using Kyoto encyclopedia of genes and genomes (KEGG) database. Single Nucleotide Polymorphism (SNP) data were retrieved from dbSNP database. SIFT and Polyphen-2 were used complementary for selecting ‘high confidence non synonymous SNP (nsSNP) based on sequence based and structure based approaches respectively. The nsSNP which were found to be damaging using both SIFT and PolyPhen-2 score analysis were further evaluated for their stability using IMutant-2.0. The functional impact of deleterious and damaging SNP were studied by modelling the homology modelling the protein using SWISS MODEL. The effect of the standard drug Zelapar was analysed in both mutated and native proteins using molecular docking studies. Results revealed that almost all the mutated proteins had a significantly lesser interaction with the drug compared to the native protein.

Keywords: Homology modeling, Parkinson’s disease, MAO-B, Single nucleotide polymorphism

Suggested Citation

S., Vishnu Sankar and Prasad, Rohit S. and Anuf, A. Ronaldo and Latha, M. S., Computational Investigations on Structural and Functional Impact of SNP in Parkinson’s Disease Associated With Human Monoamine Oxidase-B (Mao-B) (April 11, 2019). Available at SSRN: https://ssrn.com/abstract=3370116 or http://dx.doi.org/10.2139/ssrn.3370116

Vishnu Sankar S. (Contact Author)

Department of Chemistry,NSS Hindu College ( email )

Changanacherry
Kerala, KS 686102
India

Rohit S. Prasad

Department of Biotechnology,SCT college of Engineering ( email )

Thiruvananthapuram
Kerala,, 620024
India

A. Ronaldo Anuf

Department of Biotechnology,Kamaraj College of Engineering and Technology ( email )

Virudhunagar
TN 620024
India

M. S. Latha

Department of Chemistry,Sree Narayana College ( email )

Kollam
Kerala, KS 691001
India

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