DOI: 10.1101/505859Jan 6, 2019Paper

In Silico Screening and Analysis of SNPs in Human ABCB1 (MDR1) Gene

BioRxiv : the Preprint Server for Biology
Amira Hussien, Alaa A.M. Osman

Abstract

Background: ABCB1 (MDR1) is a transporter glycoprotein that has a major role in drug effluxes and resistance. Single nucleotide polymorphisms (SNPs) in ABCB1gene may affect protein expression, disease susceptibility and drug response, side effects and pharmacokinetics. The functional impact of most non-synonymous (ns) SNPs is still unclear. This study adopted a Structural bioinformatics approach to predict the effects of nsSNPs on ABCB1 structure and function. Methodology: The effects of coding nsSNPs were predicted by SIFT, PolyPhen-2, PANTHER, SNAP, PROVEAN, PhD-SNP and SNPs & GO. Prediction of protein stability changes was analyzed by I-Mutant. The conservation of amino acid positions in a protein was predicted by Consurf. NetSurfP was used to predict the surface accessibility of amino acid residue in protein structure. The impact of substitutions in protein was analyzed using Hope. Chimera was used to visualize changes in the protein 3D structure due to deleterious nsSNPs. Results: The nsSNPs of ABCB1 gene were retrieved from dbSNP database. nsSNPs were analyzed using SIFT and PolyPhen-2. To increase the accuracy of predictions, results of SIFT and PolyPhen-2 were joined and nsSNPs with PolyPhen score> 0.90 and SIFT< 0.05 w...Continue Reading

Related Concepts

Disease Susceptibility
Exons
Drug Kinetics
3-((2-nitro-4-azidophenyl)-2-aminoethyldithio)-N-succinimidyl propionate
Glutamate Transporter
Surface
ABCB1 gene
Missense Mutation
HLA-A*80 Antigen
Structure

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