In Silico Study of the Anti-MYC Potential of Lanostane-Type Triterpenes

Abstract

One of the most investigated molecular targets for anticancer therapy is the proto-oncogene MYC, which is amplified and thus overexpressed in many types of cancer. Due to its structural characteristics, developing inhibitors for the target has proven to be challenging. In this study, the anti-MYC potential of lanostane-type triterpenes was investigated for the first time, using computational approaches that involved ensemble docking, prediction of structural properties and pharmacokinetic parameters, molecular dynamics (MD), and binding energy calculation using the molecular mechanics-generalized born surface area (MM-GBSA) method. The analysis of physicochemical properties, druglikeness, and pharmacokinetic parameters showed that ligands ganoderic acid E (I), ganoderlactone D (II), ganoderic acid Y (III), ganoderic acid Df (IV), lucidenic acid F (V), ganoderic acid XL 4 (VI), mariesiic acid A (VII), and phellinol E (VIII) presented properties within the filter used. These eight ligands, in general, could interact with the molecular target favorably, with interaction energy values between −8.3 and −8.6 kcal mol −1 . In MD, the results of RMSD, RMSF, radius of gyration, and hydrogen bonds of the complexes revealed that ligands I, IV, VI, and VII interacted satisfactorily with the protein during the simulations and assisted in its conformational and energetic stabilization. The binding energy calculation using the MM-GBSA method showed better results for the MYC-VII and MYC-I complexes (−44.98 and −41.96 kcal mol −1 , respectively). These results support the hypothesis that such molecules can interact with MYC for a considerable period, which would be an essential condition for them to exert their inhibitory activity effectively.