PREDICTION OF THE EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN THE CYP2C9 ON WARFARIN METABOLISM BY IN SILICO STUDY
Keywords:Warfarin, CYP2C9, SNPs CYP2C9, In silico, Molecular modeling, Molecular docking
Objective: This study aimed to predict the effect of SNPs CYP2C9 s on the metabolic activity of S-warfarin in the body.
Methods: Molecular modeling was performed to obtain SNPs CYP2C9 and molecular docking was performed to predict the effect of SNPs CYP2C9 on the metabolic activity of S-warfarin.
Results: The results showed that wild-type CYP2C9 had the strongest binding affinity (∆G: -9.76 kcal/mol), indicating that wild-type CYP2C9 had the best metabolic activity compared to SNPs CYP2C9. There was a decrease in hydrogen bond formation in SNPs CYP2C9 and an increase in the distance between C7 S-warfarin and Fe-Heme in CYP2C9 SNPs when compared to wild-type CYP2C9
Conclusion: The decrease in binding affinity, decrease in hydrogen bond formation, and an increase in the distance between C7 S-warfarin and Fe-Heme on SNPs CYP2C9 indicated that SNPs CYP2C9 had decreased metabolic activity against S-warfarin which led to an increased risk of bleeding.
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Copyright (c) 2022 NORISCA ALIZA PUTRIANA, TAOFIK RUSDIANA, TINA ROSTINAWATI, MOHAMMAD RIZKI AKBAR, SANDRA MEGANTARA, SABRANAH HIDAYANTI
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