فهرست نشریات علمی دسترسی آزاد ایران

Cytochromes (CYP) are key players in the oxidation of xenobiotics, significantly influencing drug safety, persistence, bioactivation, and interactions between drugs and food. This study aims to develop various computational models to predict interactions of inhibitors with one of the most important CYP isoforms, CYP3A4. In this research, a dataset of CYP3A4 inhibitors was created from literature and QSAR model, HQSAR and binary QSAR model along with docking analysis, were successfully employed to investigate critical features of CYP3A4 inhibitors. A validation method was implemented to assess the accuracy of the results. The findings indicate that the energy of interaction and the overall shape of the molecules play significant roles in the inhibitory effect. Important fragments for inhibitory activity were discovered using hologram model. The docking analysis identified key amino acids in CYP3A4 that are crucial for binding the inhibitors, including Phe57, Asp76, Arg106, Arg105, Phe220, Phe108, Ala370, Ser119, and Leu482. Accurate and precise models were created using chemometric methods. The q2 and Z-score obtained for QSAR models showed that using these findings would be beneficial in drug design with little or no inhibitory effect on CYP3A4.