title: Prediction of N-Methyl-D-Aspartate Receptor GluN1-Ligand Binding Affinity by a Novel SVM-Pose/SVM-Score Combinatorial Ensemble Docking Scheme.
abstract: The glycine-binding site of the N-methyl-D-aspartate receptor (NMDAR) subunit GluN1 is a potential pharmacological target for neurodegenerative disorders. A novel combinatorial ensemble docking scheme using ligand and protein conformation ensembles and customized support vector machine (SVM)-based models to select the docked pose and to predict the docking score was generated for predicting the NMDAR GluN1-ligand binding affinity. The predicted root mean square deviation (RMSD) values in pose by SVM-Pose models were found to be in good agreement with the observed values (n = 30, r2= 0.928-0.988,  = 0.894-0.954, RMSE = 0.002-0.412, s = 0.001-0.214), and the predicted pKivalues by SVM-Score were found to be in good agreement with the observed values for the training samples (n = 24, r2= 0.967,  = 0.899, RMSE = 0.295, s = 0.170) and test samples (n = 13, q2= 0.894, RMSE = 0.437, s = 0.202). When subjected to various statistical validations, the developed SVM-Pose and SVM-Score models consistently met the most stringent criteria. A mock test asserted the predictivity of this novel docking scheme. Collectively, this accurate novel combinatorial ensemble docking scheme can be used to predict the NMDAR GluN1-ligand binding affinity for facilitating drug discovery.
authors.affiliation: Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan.|Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan.
authors.forename: Max K
authors.initials: MK
authors.lastname: Leong
authors.affiliation: Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan.
authors.forename: Ren-Guei
authors.initials: RG
authors.lastname: Syu
authors.affiliation: Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan.
authors.forename: Yi-Lung
authors.initials: YL
authors.lastname: Ding
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng