Effect of molecular properties of the protein-ligand complex on the prediction accuracy of AutoDock

Abstract

Molecular docking approach has been extensively used to predict the ligand's binding conformation in the binding pocket of protein. However, its prediction accuracy is still limited and highly dependent on target protein-ligand complexes. In this study, we investigated the effects of ligand torsion number, ligand hydrophobicity, and binding-site hydrophobicity on the prediction accuracy of Autodock, a popular molecular docking tool, combinatorially as well as respectively. A clear understanding of how these properties affect the prediction accuracy was observed when these properties were studied combinatorially rather than individually. The combination of low ligand torsion number-hydrophilic ligand-hydrophobic binding site provided the best prediction accuracy while the high ligand torsion number-hydrophilic ligand-hydrophobic binding pocket combination showed the least prediction accuracy. This study allowed us to determine the molecular properties of complex, showing relatively higher or low prediction accuracy and can be employed as a reference in the molecular docking studies using Autodock.

Keywords: AutoDock; Binding pocket hydrophobicity; Ligand hydrophobicity; Molecular docking; Prediction accuracy; Protein-ligand interactions; Torsion number.