COMPUTATIONAL EXPLORATION OF SMALL MOLECULES AS INHIBITOR TARGETTING CYTOCHROME P4502D6

Cytochrome P450 2D6 (CYP2D6) is an essential enzyme that affects the safety and effectiveness of a broad range of medications through its metabolism. We provide here an extensive in-silico investigation of new drug candidates that target CYP2D6. To find putative CYP2D6 inhibitors, we used virtual screening, structure-based drug design, molecular docking, and simulation approaches in the Biovia Discovery Studio 2022 framework. By maintaining ADMET and TOPKAT filters, a broad variety of small molecules were subjected to virtual screening. After that, the two chosen compounds, cmp1 and cmp13, were used in molecular docking studies against the 4WNU and 4XRZ proteins to evaluate binding affinities and interactions. For 2815 compounds, ADMET and TOPKAT profiling were done to get non-toxic molecules. The non-toxic molecules after filtrations were taken for the docking studies followed by molecular dynamic simulation of the best complex. The best two molecules after ADMET and TOPKAT profiling were taken for docking studies, where these results demonstrated several intriguing therapeutic options with high binding affinities and favorable interactions of compound cmp1 with the active sites of 4WNU proteins, with 26.4705 kcal/mol -CDOCKER energy and 44.37 kcal/mol -CDOCKER interaction energy. These were then selected for molecular dynamic simulations to verify the motion of each atom in the real-time environment. DeltaG_Average = -26.1570 kcal/mol was also computed as the MMPBSA energy.  The compound cmp1 was the most significant among the series as aninhibitor TargetingCYP2D6. To demonstrate the same, this molecule needed to be further examined in-vitro and in-vivo.