title: QSAR prediction of HIV-1 protease inhibitory activities using docking derived molecular descriptors.
abstract: In this study, application of a new hybrid docking-quantitative structure activity relationship (QSAR) methodology to model and predict the HIV-1 protease inhibitory activities of a series of newly synthesized chemicals is reported. This hybrid docking-QSAR approach can provide valuable information about the most important chemical and structural features of the ligands that affect their inhibitory activities. Docking studies were used to find the actual conformations of chemicals in active site of HIV-1 protease. Then the molecular descriptors were calculated from these conformations. Multiple linear regression (MLR) and least square support vector machine (LS-SVM) were used as QSAR models, respectively. The obtained results reveal that statistical parameters of the LS-SVM model are better than the MLR model, which indicate that there are some non-linear relations between selected molecular descriptors and anti-HIV activities of interested chemicals. The correlation coefficient (R), root mean square error (RMSE) and average absolute error (AAE) for LS-SVM are: R=0.988, RMSE=0.207 and AAE=0.145 for the training set, and R=0.965, RMSE=0.403 and AAE=0.338 for the test set. Leave one out cross validation test was used for assessment of the predictive power and validity of models which led to cross-validation correlation coefficient QUOTE of 0.864 and 0.850 and standardized predicted relative error sum of squares (SPRESS) of 0.553 and 0.581 for LS-SVM and MLR models, respectively.
authors.affiliation: Chemometrics Laboratory, Faculty of Chemistry, University of Mazandaran, Babolsar 47416-95447, Iran. Electronic address: mhfatemi@umz.ac.ir.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Fatemi
authors.affiliation: Chemometrics Laboratory, Faculty of Chemistry, University of Mazandaran, Babolsar 47416-95447, Iran.
authors.forename: Afsane
authors.initials: A
authors.lastname: Heidari
authors.affiliation: Department of Bioinformatics, Laboratory of Chemoinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Gharaghani
mesh_terms: D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D016018:Least-Squares Analysis; D008024:Ligands; D016014:Linear Models; D008962:Models, Theoretical; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D012015:Reference Standards; D060388:Support Vector Machine
chemical_list: D017320:HIV Protease Inhibitors; D008024:Ligands; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1
keywords: AutoDock; Hybrid docking; Molecular descriptor; Quantitative structure activity relationship