Molecular docking and dynamics of Annona muricata L. megastigmanes and metabolites on enzyme markers of breast cancer and their effect on heterodimer formation

Abstract

Objective: To analyze the molecular docking of secondary metabolites of soursop on the enzyme markers of breast cancer. Design/Methodology/Approach: Crystals of PARP2 and PRMT5 enzymes were obtained from RCSB-PDB. Both crystals were processed using bioinformatic tools (e.g., SWISS-MODEL, UCSF-Chimera, and ScanProsite), prior to molecular docking and dynamics. The Annona muricata L. metabolites were obtained from Pubchem for their use in several in silico analysis. The Autodock algorithm was used to obtain the molecular docking. Once the most stable conformations were obtained for the ligands of each enzyme, their complexes were subjected to 10 ns of molecular dynamics using GROMACS. Meanwhile, the HPF1-PARP2 and the MEP50-PRMT5 heterodimeric interactions were carried out using the HDOCK server. Finally, the possible biotransformation reactions were studied using QSAR models. Results: The kaempferol-3-O-rutinoside metabolite showed potential biopharmaceutical use as an inhibitor of the PARP2 enzyme. The coreximin ligand showed potential biopharmaceutical use as an inhibitor of the PRMT5 enzyme. The inhibitor impacted the PRMT5-MEP50 interaction. The QSAR models indicated that methylation, O-glucuronidation, and O-dealkylation were the most likely biotransformation reactions among the metabolites with the highest degree of inhibition. Study Limitation/Implications: in silico analysis on inhibition of key proteins. Findings/Conclusions: The kaempferol-3-O-rutinoside chemical compound showed potential as a PARP2 inhibitor. The coreximin chemical compound showed potential as a PRMT5 inhibitor. The protein-protein interaction between PRMT5 and MEP50 was impacted by the inhibitor; however, this was not the case with the PARP2 enzyme.