Exquisite binding interaction of 18β-Glycyrrhetinic acid with histone like DNA binding protein of Helicobacter pylori: A computational and experimental study

The Histone-like DNA binding protein is one of the most abundant nucleoid associated protein expressed by human gastric-pathogen, Helicobacter pylori (H. pylori). The protein-referred here as Huphas been recognized as a potential drug target for developing therapeutic strategies against H. pylori. However, no attempts have been made, so far, to perturb the functioning of Hup through small molecules. As a first step in this direction, we virtually screened a natural product library containing 56 drug-like bioactive compounds and rationally selected 18 beta-Glycyrrhetinic acid (GrA) for further computational and experimental testing of its binding interaction with Hup at the molecular level. The binding modes for GrA-Hup complexes were identified using in silico molecular docking methods and their solution dynamics and stability were evaluated using long run molecular dynamics simulations. Next, we experimentally demonstrated this binding interaction using fluorescence-quenching and ligand based NMR approaches. The fluorescence quenching and NMR titration experiments resulted into apparent dissociation constant (k(D)) for GrA-Hup binding equal to 87 +/- 12 mu M and 36.6 +/- 1.5 mu M, respectively. The various results demonstrate that GrA exhibits an exquisite binding interaction with Hup and would serve as an important molecular scaffold for developing next generation anti-H. pylori agents. (C) 2020 Published by Elsevier B.V.