Detection of The Effect of CYP2C19*4 Mutation on Clopidogrel Response by In Silico Methods

Abstract

Single nucleotide polymorphisms cause amino acid change, and protein structure and function are changed. Thus, the patient improves drug resistance and does not respond to therapy. Clopidogrel is an antiplatelet drug and is used for cardiovascular disease therapy such as heart failure, atherosclerosis, and myocardial infarction.CYP2C19 gene is a CYP450 enzyme and metabolizes clopidogrel. Polymorphism of the CYP2C19 gene causes clopidogrel response. A homology modeling study was carried out using the Swiss-Model database and the Chimera program. The selection of models was made with the evaluation of the QMEAN values of the three-dimensional structures. The physicochemical properties of the wild type and CYP2C19*4 mutant type were analyzed by the ExPASy-ProtParam Portal. The effects of the mutation on the protein structure were performed by the HOPE database. The HDock program was used to demonstrate interactions between clopidogrel and wild-type protein and, mutant type protein. Mutation of the residue might disturb this function. This mutation causes the loss of interactions and affects the drug response. In this study, it was shown that Clopidogrel drug interactions between mutant type protein by docking study. Possible drug conformation is designed for the effective treatment of patients carrying the common mutation.

Keywords

• Heart failure
• drug resistance
• clopidogrel
• homology modeling
• single nucleotide polymorphism (SNP)

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