In silico docking and Molecular Dynamic (MD) simulations studies of selected phytochemicals against Human Glycolate Oxidase (hGOX) and Oxalate oxidase (OxO).

Abstract

Globally, Urolithiasis is the most prevalent urological problem which affects the populations across the ages and races. In recent years, several phytochemicals are being investigated to improve the efficacy and safety of anti-urolithiasis formulations. To develop drugs based on traditional medicines, it is essential to understand the molecular mechanism of action of these drugs. We present the results of in silico docking and molecular dynamic (MD) simulation studies on selected phytochemical including catechin, epicatechin, gallic acid, gallocatechin, epigallocatechin, epigallocatechin 3-o-gallate, 4-methoxy-nor-securine, nor-securinine, and fisetin with human glycolate oxidase (hGOX) and oxalate oxidase (OxO). Gallic acid, gallocatechin and fisetin showed better docking scores than the rest. In MD simulation analysis, stable interactions of the gallic acid with hGOX and OxO; gallocatechin and fisetin with hGOX were observed. It was found that, gallic acid stably interacts withTYR26, LYS 236, ARG 315, and ASP 291 residues of hGOX. On other hand, gallic acid stably interacs with GLU 58 residue of OxO. Gallocatechin, forms stable interactions with TYR 26, ASP 170, ARG 167 and THR 161 of HGOX. In MD simulations, fisetin stably interacted with TYR 26, TRP110 and ARG 263 as we predicted in molecular docking. None of the interactions was formed during the MD simulation of OxO with gallocatechin and fisetin. Together, these results suggest that gallic acid, gallocatechin and fisetin are the potential candidates for the development of phytochemicals for the management of urolithiasis in humans.