title: QSAR modeling and molecular interaction analysis of natural compounds as potent neuraminidase inhibitors.
abstract: Different QSAR models of 40 natural compounds as neuraminidase inhibitors (NIs) are developed to comprehend chemical-biological interactions and predict activities against neuraminidase (NA) from Clostridium perfringens. Based on the constitutional, topological and conformational descriptors, R(2) and Q(2) values of the obtained SRA model are 0.931 and 0.856. The R(2) and Q(2) values of the constructed HQSAR and almond models are 0.903 and 0.767, 0.904 and 0.511, respectively. Based on the pharmacophore alignment, R(2) and Q(2) values of the optimal CoMSIA model are 0.936 and 0.654. Moreover, Rtest(2) and Qext(2) of values of SRA, HQSAR, almond and CoMSIA models are 0.611 and 0.565, 0.753 and 0.750, 0.612 and 0.582, 0.582 and 0.571, respectively. So, QSAR models have good predictive capability. They can be further used to evaluate and screen new compounds. Moreover, hydrogen bonds and electrostatic factors have high contributions to activities. To understand molecular interactions between natural compounds and NA from Clostridium perfringens, molecular docking is investigated. The docking results elucidate that Arg266, Asp291, Asp328, Tyr485, Glu493, Arg555, Arg615 and Tyr655 are especially the key residues in the active site of 2bf6. Hydrogen bonds and electrostatics are key factors, which impact the interactions between NIs and NA. So, the influential factors of interactions between NIs and NA in the docking results are in agreement with the QSAR results.
authors.affiliation: Department of Chemistry and Chemical Engineering, Sichuan University of Arts and Science, Sichuan Dazhou 635000, China. wy7472@126.com.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Mei
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D009439:Neuraminidase