3D QSAR studies of AChE inhibitors based on molecular docking scores and CoMFA

Three-dimensional quantitative structure–activity relationship (3D QSAR) studies were performed on acetylcholinesterase (AChE) inhibitors, based on molecular docking scores obtained by using FlexX and FlexiDock and comparative molecular field analysis (CoMFA). The docking scores were used as molecular descriptors along with the steric and electrostatic field values of CoMFA, for partial least square (PLS) analysis. The high leave one out (LOO) cross-validated correlation coefficient (q2 = 0.714) reveals that the model is a useful tool for the prediction of test set as well as newly designed structures against AChE activity. The superimposed CoMFA models on the receptor site of AChE are guiding the design of potential inhibitory structures directed against AChE activity.

Graphical abstractComparison of the FlexX and FlexiDock, ligand–protein complexes of compound 3B. The bound inhibitor is shown as ball and stick model. Magenta colored ligand is FlexX docked structure where orange color structure is FlexiDock. The backbone of the protein structure is rendered as shaded ribbon with color by property and the labeled protein residues are in capped stick model with color by atom.Figure optionsDownload full-size imageDownload as PowerPoint slide