Investigating the Propagating effects of Griseofulvin on Erectile Dysfunction: A Comprehensive Computational and Molecular Docking Study on Human Phosphodiesterase 5 proteins (1UDT and 1UDU).

Abstract

Erectile dysfunction (ED) is a prevalent condition affecting a significant portion of the male population. This research delves into the potential link between Griseofulvin, a known antifungal medication, and its impact on erectile function. A comprehensive computational approach was employed. Optimization of griseofulvin was carried out using the highly reputable density functional theory (DFT) with the B3LYP functional and 6–31*G(d,p) using water and ethanol as the solvents of interest. We explored the interactions of Griseofulvin with Human Phosphodiesterase 5 proteins (PDE5), specifically targeting the crystal structures 1UDT and 1UDU. Molecular docking studies provided valuable insights into the binding mechanisms of Griseofulvin with PDE5, shedding light on potential allosteric modulation and conformational changes. Further molecular docking studies were carried out on other popular antifungal drugs like amphotericin, terbinafine and ketoconazole in order to compare their interactions with 1UDT and 1UDU with that of griseofulvin. Through an array of computational analyses, including molecular dynamics simulations and binding free energy calculations, we aimed to elucidate the propagating effects of Griseofulvin on the catalytic activity and structural stability of PDE5. The findings from this research could contribute to a deeper understanding of the molecular mechanisms underlying Griseofulvin's impact on erectile function, potentially opening avenues for the development of novel therapeutic interventions for ED.