Molecular docking and dynamics simulation analysis of PDE5 inhibitor candidates for erectile dysfunction treatment.

Abstract

Objective: Molecular docking studies were conducted to assess the binding affinities of five potential inhibitor candidates [PDB (Protein Data Bank) ID: 6L6E] against Phosphodiesterase 5 (PDE5), with Sildenafil used as the reference compound. The aim of this study is to reveal the potential inhibitory role of plant-derived compounds compared to Sildenafil, a PDE5 inhibitor.

Materials and methods: Autodock Vina v. 1.2.5 software was used to dock the protein and each ligand individually. Molecular dynamics simulations assessed the binding affinity of two compounds to the Phosphodiesterase 5A1 (PDE5 A1) enzyme and were carried out using GROMACS 2022.2 RESULTS: Boesenbergin A exhibited the highest affinity at -8.8 kcal/mol, followed by Ginkolide B at -8.5 kcal/mol, Sildenafil at -8.1 kcal/mol, Montanol at -7.8 kcal/mol, Beta-sitosterol at -7.1 kcal/mol, and Eugenol acetate at -6.9 kcal/mol, ranked in descending order. As a result of molecular docking studies, molecular dynamic simulations were performed for Boesenbergin A, which has the highest affinity, and Sildenafil, which is the standard molecule.

Conclusions: Among the two ligands tested, Boesenbergin A exhibited superior binding affinity, surpassing even the standard molecule, Sildenafil. This suggests their potential for modulating enzyme activity and potential relevance in erectile dysfunction treatment.