4D-QSAR study of flavonoid derivatives with MCET method

Abstract

The Molecular Conformer Electron Topological (MCET) method was performed for the identification of the pharmacophore (Pha) group and predicting inhibitory activity of 42 flavonoid ligands on gamma-aminobutyric acid/benzodiazepine receptor complex (GABAA/BZR). In this method, Electron Topological Matrix (ETM) was used to visualize 3D structural descriptors. Multiple comparisons of ETM matrices for all flavonoid compounds allow us to define Pha-structure. Genetic algorithm (GA)-Partial Least-Squares (PLS) methods were performed to construct QSAR model and to select most important descriptors of the training set (32 compounds) and test set (10 compounds). The GA-PLS based model showed good results, q 2 = 0.808 and r 2 test = 0.775 with high internal and external validation. The developed model can help to understand the inhibitory mechanism.

Optimal Division of Molecules Into Training And Test Sets With A New Tool To Predict Pharmacophore In 3D-QSAR

“…Molecular conformers were determined by using MMFF with Spartan'10 program and quantum chemical calculations were made with Hartree-Fock 6-31G*. For each conformer to be used in MCET method, '*.txt' les produced from Spartan were converted to "Electron Topological Matrix" (ETM) les with ETM-Program (ETM-P)[37][38][39][40].…”