title: Molecular dynamics directed CoMFA studies on carbocyclic neuraminidase inhibitors.
abstract: Zanamivir is the known potent anti-influenza agent targeting the key enzyme neuraminidase that cleaves sialic acid from cell receptors allowing release of newly formed virions. Molecular dynamics simulation was carried out to determine the dynamic behavior of Zanamivir upon its binding to flexible loops of neuraminidase and to analyse its interactions in the bioactive state. Neuraminidase exhibits wide range of affinity with structurally similar compounds. CoMFA study was used to determine quantitative structure-activity relationship for 36 carbocyclic Neuraminidase inhibitors (NIs). The CoMFA model was also successfully built using cross-validated r²cv = 0.580 and r²pred = 0.638.
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Chavan
authors.forename: Sagar
authors.initials: S
authors.lastname: Bhayye
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology; D016018:Least-Squares Analysis; D056004:Molecular Dynamics Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics; D053243:Zanamivir / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D009439:Neuraminidase; D053243:Zanamivir