Consensus combining outcomes of multiple ensemble dockings: examples using dDAT crystalized complexes

Docking using different programs provides more reliable information about the interaction of molecules than data obtained in a single program. An exponential consensus ranking (ECR) was developed to combine scoring functions across docking programs differing in efficiencies and scales of measurements. The ECR method was adapted to merge results of re- and cross-dockings (i.e., ensemble docking) made in multiple docking programs. Adapted ECR consisted of four consecutive steps: 1- determination of scoring functions for a ligand with a series of macromolecules in multiple docking programs; 2- ranking of the scoring functions per macromolecule in each program; 3- combining the ranking across the programs creating a ranking per macromolecule; 4- averaging the ranking per macromolecule creating a final ranking. This last step incorporated the heterogeneity of the macromolecule conformations in the consensual score. The final ranking based on the adapted ECR represents relative affinity of a series of ligands to a macromolecule on average. As an example, a ranking of the average affinity of antidepressants and other ligands to the Drosophila melanogaster dopamine transporter (dDAT) was presented. Adapted ECR generated a ranking similar to that based on the affinity constant of each ligand obtained from the literature. • A final ranking of the average relative affinity of different ligands to the dDAT. • A consensus method combining multiple ensemble dockings. • A complete protocol to make re-docking and cross-docking using Autodock Vina, Gold and DockThor.