Fungicides Inhibition Analysis by Molecular Docking and Sensitivity Testing of Penicillium italicum

Blue mold, caused by Penicillium. italicum, is one of the most damaging postharvest diseases of citrus fruit. P. italicum Sterol 14α-demethylase (PiCYP51), an important enzyme in membrance sterol biosynthesis, is a key target of antifungal compounds for citrus disease caused by P. italicum. The three-dimensional structure of PiCYP51 from P. italicum Chinese isolate (HS-1) was constructed through homology modeling basing on the crystal structure of human CYP51. After molecular dynamics (MD) simulation, the refined model was assessed by PROCHECK on the quality. Following evaluation on the reliability was performed by investigating the binding interaction of two commercial sterol 14α-demethylase inhibitors (DMIs) with the enzyme. The binding mode predicted by the molecular docking revealed that the DMIs interacted with PiCYP51 mainly through hydrogen-bonding and hydrophobic interactions. Furthermore, the results were compatible with the detected EC50 values, which were determined as 0.25 and 0.31mg/L for tebuconazole and diniconazole. The binding mode of antifungal agents with PiCYP51 can provide references for DMIs optimization, virtual screening, or de novo antifungal compounds design.