In-silico mining of SNP-effects on structural properties of CYP2C9 and their consequences

摘要

CYP2C9 is one of the important members of CYP450 family, which is well known to play very important and crucial role in drug and toxic compounds metabolism. CYP2C9 alone is responsible for the metabolism of more than 20% drugs. Today list of drugs are known as drug designed to be metabolized by CYP2C9. It has been observed that presence of population specific, non-synonymous SNPs in CYP2C9 alter the rate of drug metabolism and as a consequence, drug produce abnormal response, i.e.-variable drug response, in individuals belongs to different population group. In current work by using CYP2C9*2 (mutant1 144Arg>Cys) and CYP2C9*3 (mutant2 359Ile>Leu) SNP-variant of CYP2C9 we try to elucidated the alterations in physiochemical and structural properties in compare with the properties of wild type CYP2C9. Further we also try to observe the effect of altered features on molecular folding and interaction through MD simulation, and docking between CYP2C9 and its two variants (CYP2C9*2 and CYP2C9*3) with warfarin, which is a one of well-known anticoagulant and metabolized by CYP2C9.