Molecular docking study of the affinity of CYP2C9 and CYP2D6 for imrecoxib

With the aid of the automatic molecular docking, the affinity of CYP2C9 and CYP2D6 for imrecoxib was studied by InsightII/Affinity program. The results indicate that CYP2C9-imrecoxib complex has higher stability and stronger affinity because CYP2C9 has more favorable interaction energy (-62.72 kcal/mol) and higher Ludi score (610) with imrecoxib than CYP2D6 (-50.22 kcal/mol and 551) and this is consistent with the results of the kinetic experiments by Li et al. By analyzing the theoretical results combined with the experimental ones, we suggest that the affinity difference is caused by the difference of the structure between CYP2C9 and CYP2D6, and the most important residues for enzyme-substrate complexes, such as Phe476, Asn204, Phe100, Leu366 and Arg108 of CYP2C9 and Phe120, Glu216, and Phe483 of CYP2D6 were also identified.