PREDICTION OF THE EFFECT OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN THE CYP2C9 ON WARFARIN METABOLISM BY IN SILICO STUDY
Norisca Aliza Putriana, Taofik Rusdiana, Tina Rostinawati, Mohammad Rizki Akbar, Sandra Megantara, SABRANAH HIDAYANTI · International Journal of Applied Pharmaceutics · 2022
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.