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Ligand Efficiency in Relation to 3D Physicochemical Characters of Novel HIV-1 Vif Antagonist: An Approach in The Optimization of HIV Drugs
Abstract
Abstract
Ligand efficiency is a design framework commonly used in drug discovery. Thirty-six (36) newly discovered 1,2,3-triazole analogues as potent new inhibitors of HIV-1 Vif were subjected to quantitative structure-property relationship (QSPR) modeling to predict their ligand efficiencies (LE) in an attempt to improve/optimize it by using some numerical data of HIV-1 Vif inhibitors based on their physical and chemical properties (descriptors). Various 3D physicochemical properties or descriptors were calculated from the developed structures using ChemoPy descriptor software. The Kennard-Stone technique was also used to split the dataset into training and test sets. Due to the strong internal and external validation metrics, the model created from the training set while employing multiple stepwise multiple linear regression is good (R2train = 0.92961, R2 adjusted = 0.85922, PRESS = 0.00108, average R2m (LOO-train) = 0.63422, Q2cv = 0.6945, R2pred = 0.93887, R2test = 0.6945) that met the model acceptance criteria. The proposed model, when validated by internal and external validation, has good robustness and predictive ability. This model can be applied in rational drug design to optimize the ligand efficiency metrics of drugs against HIV based on 1,2,3-triazoles scaffold.
Keywords: Ligand efficiency, QSPR, 1,2,3-triazoles, HIV, HIV-1 Vif inhibitors, Stepwise-MLR
Citation: Louis Okeibunor Odeigah, Olalekan Ayodele Agede, Ismaila Aberi Obalowu, Yahkub Babatunde Mutalub and George Oche Ambrose. Ligand Efficiency in Relation to 3D Physicochemical Characters of Novel HIV-1 Vif Antagonist: An Approach in The Optimization of HIV Drugs. Research & Reviews: A Journal of Drug Formulation, Development and Production. 2022; 9(3): 44–53p
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