Molecular insight in to the selective inhibition of Phosphodiesterase 5A by fulvic acid (principal constituent of shilajit): Molecular dynamics simulation evidences

The phosphodiesterase 5A, hydrolyzes cGMP, is expressed in the corpus cavernosum and main player behind erectile dysfunction. Inhibition of PDE5A is therefore a natural target in treatments of erectile dysfunction. Fulvic acid which is a principal constituent of shilajit (a natural substance used against erectile dysfunction) was found to be stably bound to Q pocket of catalytic site of PDE5A as evidenced by molecular dynamic simulation studies. The binding of fulvic acid is mainly contributed by the hydrogen bonding with non-conserved residues in PDE5A such as Asp 764, Leu 765, Ser 766, Ala 767, Ile 768 and Gln 817 along with hydrophobic contact with residues Phe 820, Leu 804, Phe 786, Val 782 and Ile 778 of Q pocket.