Pairwise Performance Comparison of Docking Scoring Functions: Computational Approach Using InterCriteria Analysis

Scoring functions are key elements in docking protocols as they approximate the binding affinity of a ligand (usually a small bioactive molecule) through calculating its interaction energy with a biomacromolecule (usually protein). In this study we present a pairwise comparison of scoring functions applying a multi-criterion decision-making approach based on InterCriteria analysis (ICrA). As criteria, the five scoring functions implemented in MOE (Molecular Operating Environment) software were selected and their performance on a set of protein-ligand complexes from the PDBbind database were compared. The following docking outputs were used: the best docking score; the lowest root-mean-square deviation (RMSD) between the predicted pose and the co-crystalized ligand; the RMSD between the best docking score pose and the co-crystalized ligand; the docking score of the pose with the lowest RMSD to the co-crystalized ligand. The impact of ICrA thresholds on the relations between the scoring functions was investigated. A correlation analysis was also performed and juxtaposed to ICrA. Our results reveal the lowest RMSD as the best performing docking output and two scoring functions (Alpha HB and London dG) as having the highest comparability. The proposed approach can be applied to any other scoring functions and protein-ligand complexes of interest.