title: Molecular Docking Guided Comparative GFA, G/PLS, SVM and ANN Models of Structurally Diverse Dual Binding Site Acetylcholinesterase Inhibitors.
abstract: Recently discovered 42 AChE inhibitors binding at the catalytic and peripheral anionic site were identified on the basis of molecular docking approach, and its comparative quantitative structure-activity relationship (QSAR) models were developed. These structurally diverse inhibitors were obtained by our previously reported high-throughput in vitro screening technique using 384-well plate's assay based on colorimetric method of Ellman. QSAR models were developed using (i) genetic function algorithm, (ii) genetic partial least squares, (iii) support vector machine and (iv) artificial neural network techniques. The QSAR model robustness and significance was critically assessed using different cross-validation techniques on test data set. The generated QSAR models using thermodynamic, electrotopological and electronic descriptors showed that nonlinear methods are more robust than linear methods, and provide insight into the structural features of compounds that are important for AChE inhibition.
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar-160 062, Punjab, India phone: 0091-172-2214682-2019, fax: 0091-172-2214692;
authors.forename: Shikhar
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Biosciences, Biocity, Åbo Akademi University, Artillerigatan 6A, FI 20520, Turku, Finland.
authors.forename: Adyary
authors.initials: A
authors.lastname: Fallarero
authors.affiliation: Department of Biosciences, Biocity, Åbo Akademi University, Artillerigatan 6A, FI 20520, Turku, Finland.
authors.forename: Mikko J
authors.initials: MJ
authors.lastname: Vainio
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar-160 062, Punjab, India phone: 0091-172-2214682-2019, fax: 0091-172-2214692;
authors.forename: P
authors.initials: P
authors.lastname: Saravanan
authors.affiliation: Department of Biosciences, Biocity, Åbo Akademi University, Artillerigatan 6A, FI 20520, Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Santeri Puranen
authors.affiliation: Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, FI-00014, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Järvinen
authors.affiliation: Department of Biosciences, Biocity, Åbo Akademi University, Artillerigatan 6A, FI 20520, Turku, Finland.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Johnson
authors.affiliation: Department of Biosciences, Biocity, Åbo Akademi University, Artillerigatan 6A, FI 20520, Turku, Finland.
authors.forename: Pia M
authors.initials: PM
authors.lastname: Vuorela
authors.affiliation: Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar-160 062, Punjab, India phone: 0091-172-2214682-2019, fax: 0091-172-2214692;. cgopimohan@yahoo.com, cmohan@niper.ac.in.
authors.forename: C Gopi
authors.initials: CG
authors.lastname: Mohan
keywords: AChE; ANN; Docking; G/PLS; GFA; QSAR; SVM