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
Date Written: April 11, 2019
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
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