title: Combining docking, scoring and molecular field analyses to probe influenza neuraminidase-ligand interactions.
abstract: In this project, several docking conditions, scoring functions and corresponding protein-aligned molecular field analysis (CoMFA) models were evaluated for a diverse set of neuraminidase (NA) inhibitors. To this end, a group of inhibitors were docked into the active site of NA. The docked structures were utilized to construct a corresponding protein-aligned CoMFA models by employing probe-based (H+, OH, CH3) energy grids and genetic partial least squares (G/PLS) statistical analysis. A total of 16 different docking configurations were evaluated, of which some succeeded in producing self-consistent and predictive CoMFA models. However, the best model coincided with docking the ionized ligands into the hydrated form of the binding site via PLP1 scoring function (r2LOO=0.735, r2PRESS against 24 test compounds=0.828). The highest-ranking CoMFA models were employed to probe NA-ligand interactions. Further validation by comparison with a co-crystallized ligand-NA crystallographic structure was performed. This combination of docking/scoring/CoMFA modeling provided interesting insights into the binding of different NA inhibitors.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Queen Rania Street, Amman 11942, Jordan.
authors.forename: Areej M
authors.initials: AM
authors.lastname: Abu Hammad
authors.forename: Fatma U
authors.initials: FU
authors.lastname: Afifi
authors.forename: Mutasem O
authors.initials: MO
authors.lastname: Taha
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007251:Influenza, Human / Q000201:enzymology*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D009439:Neuraminidase