Interactions of coreopsin with CYP3A4/CYP2D6 by multi-spectroscopy analysis and computer simulation

Abstract In this study, different spectral methods, molecular docking, dynamics simulation are applied for revealing the binding mechanisms of coreopsin to CYP3A4/CYP2D6. Coreopsin quenches CYPs mainly in static mode and supplement in dynamic mode. The Kb values of the CYPs are within 104 ~ 105 L·mol-1, indicating that coreopsin has moderate and stronger affinity with CYPs. Meanwhile, the binding ability of CYP3A4- coreopsin is stronger than that of CYP2D6-coreopsin at the same temperature. It is also demonstrated that coreopsin has significant effects on the secondary structure of CYPs through hydrogen bonds together with van der Waals force. The optimal binding mode, specific binding sites of the two complexes are determined by molecular docking, and stability of the two complexes formed by coreopsin and CYPs are verified using molecular simulation dynamics.