In silico identification and analysis of potential inhibitors for acid phosphatase, HppA from Helicobacter pylori

Abstract

AbstractHelicobacter pylori is the most common cause of gastric ulcers and is associated with gastric cancer. The enzyme HppA of class C nonspecific acid phosphohydrolases (NSAPs) of H. pylori plays a crucial role in the electron transport chain. Herein, we report an in silico homology model of HppA consisting of a monomeric α + β model. A high throughput structure‐based virtual screening approach yielded potential inhibitors against HppA with higher binding energies. Further analyses of molecular interaction maps and protein–ligand fingerprints, followed by molecular mechanics‐generalized Born surface area (MM‐GBSA) end point binding energy calculations of docked complexes, resulted in the detection of top binders/ligands. Our investigations identified potential substrate‐competitive small molecule inhibitors of HppA, with admissible pharmacokinetic properties. These molecules may provide a starting point for developing novel therapeutic agents against H. pylori.