Molecular Dynamics and MM-PBSA Studies for Deciphering Molecular Interactions of Valproic Acid with CYP2C9 Mutants F114L and I207T

Valproic Acid (VPA) is a widely used drug, particularly in neuropsychiatric disorders, while showing promise other types of diseases such as cancer. VPA metabolism via cytochrome P450 (CYP) pathway responsible from only ~10% the total drug dose. However, due to high risk severe adverse reactions liver and pancreas, interaction with CYP2C9 remains be delineated chiefly mutants. Hence, here we implemented molecular dynamics study, followed by MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method based relative binding energy estimation understand how F114L I207T mutants changed their mode towards comparison wild type (WT) CYP2C9. Results indicated that have showed significant decrease energy, compared WT, there were clear shift occupied amino acids for vs WT. Overall, first time literature, this novel interacting reported. Limitations future perspective data also discussed.