He Docking and molecular dynamics of megastigmans and Annona muricata alkaloids on breast cancer marker enzymes and their effect on heterodimer formation

Abstract

Objective: To analyze the molecular docking of secondary metabolites of soursop on marker enzymes of breast cancer.

Design/methodology/approach: Crystals of PARP2 and PRMT5 enzymes were obtained from RCSB-PDB. Both crystals were processed with bioinformatic tools such as SWISS-MODEL, UCSF-Chimera and ScanProsite, preparing them for docking and molecular dynamics. Annona muricata metabolites were used in the various in silico analyzes and obtained from Pubchem. Molecular docking was performed with the Autodock algorithm. Once the most stable conformations with the ligands for each enzyme were obtained, their complexes were subjected to 10 ns of molecular dynamics using GROMACS. On the other hand, HPF1-PARP2 and MEP50-PRMT5 heterodimeric interactions were performed using the HDOCK server. Finally, the possible biotransformation reactions were studied using QSAR models.

Results: The kaempferol-3-O-rutinoside metabolite showed potential use as a biopharmaceutical for the inhibition of the PARP2 enzyme. The coreximin ligand showed a potential use as a biopharmaceutical for the inhibition of the PRMT5 enzyme. The interaction between PRMT5 and MEP50 was affected by the presence of the inhibitor. The QSAR models indicated that the most probable biotransformation reactions were those of methylation, O-glucuronidation and O-dealkylation for the metabolites with the highest degree of inhibition.

Limitations on study/implications: in silico analysis on inhibition of key proteins.

Findings/conclusions: The chemical compund kaempferol-3-O-rutinosido showed a potential use as a PARP2 inhibition drug. The chemical compund coreximine showed a potential use as a PRMT5 inhibition drug. The protein-protein interaction between PRMT5 and MEP50 was afected for the inhibitor presence, not so with PARP2 enzyme.