caa a22 4500 445879122 CHVBK 20180317145537.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11030-010-9269-y doi (NATIONALLICENCE)springer-10.1007/s11030-010-9269-y Integration-mediated prediction enrichment of quantitative model for Hsp90 inhibitors as anti-cancer agents: 3D-QSAR study [Elektronische Daten] [Kuldeep Roy, Supriya Singh, Anil Saxena] The present study describes a systematic 3D-QSAR study consisting of pharmacophore modeling, docking, and integration of ligand-based and structure-based drug design approaches, applied on a dataset of 72 Hsp90 inhibitors as anti-cancer agents. The best pharmacophore model, with one H-bond donor (HBD), one H-bond acceptor (HBA), one hydrophobic_aromatic (Hy_Ar), and two hydrophobic_aliphatic (Hy_Al) features, was developed using the Catalyst/HypoGen algorithm on a training set of 35 compounds. The model was further validated using test set, external set, Fisher's randomization method, and ability of the pharmacophoric features to complement the active site amino acids. Docking analysis was performed using Hsp90 chaperone (PDB-Id: 1uyf) along with water molecules reported to be crucial for binding and catalysis (Sgobba etal. ChemMedChem 4:1399-1409, 2009). Furthermore, an integration of the ligand-based as well as structure-based drug design approaches was done leading to the integrated model, which was found to be superior over the best pharmacophore model in terms of its predictive ability on internal [integrated model 2: R (train) = 0.954, R (test) = 0.888; Hypo-01: R (train) = 0.912 and R (test)= 0.819] as well as on external data set [integrated model 2: R (ext.set) = 0.801; Hypo-01: R (ext.set) = 0.604]. Springer Science+Business Media B.V., 2010 QSAR nationallicence Pharmacophore nationallicence Catalyst nationallicence Hsp90 nationallicence Integration nationallicence Cancer nationallicence Hsp90 : Heat shock protein 90 nationallicence CADD : Computer-aided drug design nationallicence VS : Virtual screening nationallicence PBVS : Pharmacophore-based VS nationallicence SBVS : Structure-based VS nationallicence Roy Kuldeep Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, 226001, Lucknow, India aut Singh Supriya Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, 226001, Lucknow, India aut Saxena Anil Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, 226001, Lucknow, India aut Molecular Diversity Springer Netherlands 15/2(2011-05-01), 477-489 1381-1991 15:2<477 2011 15 11030 https://doi.org/10.1007/s11030-010-9269-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-010-9269-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Roy Kuldeep Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, 226001, Lucknow, India aut NATIONALLICENCE 700 1- Singh Supriya Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, 226001, Lucknow, India aut NATIONALLICENCE 700 1- Saxena Anil Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, 226001, Lucknow, India aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/2(2011-05-01), 477-489 1381-1991 15:2<477 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer