title: Molecular Docking studies of D2 Dopamine receptor with Risperidone derivatives.
abstract: In this work, 3D model of D2 dopamine receptor was determined by comparative homology modeling program MODELLER. The computed model's energy was minimized and validated using PROCHECK and Errat tool to obtain a stable model structure and was submitted in Protein Model Database (PMDB-ID: PM0079251). Stable model was used for molecular docking against Risperidone and their 15 derivatives using AutoDock 4.2, which resulted in energy-based descriptors such as Binding Energy, Ligand Efficiency, Inhib Constant, Intermol energy, vdW + Hbond + desolv Energy, Electrostatic Energy, Total Internal Energy and Torsional Energy. After that, we have built quantitative structure activity relationship (QSAR) model, which was trained and tested on Risperidone and their 15 derivatives having activity value pKi in µM. For QSAR modeling, Multiple Linear Regression model was engendered using energy-based descriptors yielding correlation coefficient r2 of 0.513. To assess the predictive performance of QSAR models, different cross-validation procedures were adopted. Our results suggests that ligand-receptor binding interactions for D2 employing QSAR modeling seems to be a promising approach for prediction of pKi value of novel antagonists against D2 receptor.
authors: Department of Pharmacology and Therapeutics, King George's Medical University Erstwhile CSMMU, Lucknow 226003, UP,India.
authors: Kiran
authors: K
authors: Bhargava
authors: Department of Pharmacology and Therapeutics, King George's Medical University Erstwhile CSMMU, Lucknow 226003, UP,India.
authors: Rajendra
authors: R
authors: Nath
authors: Biotech Park, Lucknow-226021, UP, India.
authors: Prahlad Kumar
authors: PK
authors: Seth
authors: Department of Pharmacology and Therapeutics, King George's Medical University Erstwhile CSMMU, Lucknow 226003, UP,India.
authors: Kamlesh Kumar
authors: KK
authors: Pant
authors: Department of Pharmacology and Therapeutics, King George's Medical University Erstwhile CSMMU, Lucknow 226003, UP,India.
authors: Rakesh Kumar
authors: RK
authors: Dixit
keywords: AutoDock; D2 dopamine receptor; Docking; Risperidone analogues; Schizophrenia