Ligand- and receptor-based docking with LiBELa

Methodologies on molecular docking are constantly improving. The problem consists on finding an optimal interplay between the computational cost and a satisfactory physical description of ligand-receptor interaction. In pursuit of an advance in current methods we developed a mixed docking approach combining ligand- and receptor-based strategies in a docking engine, where tridimensional descriptors for shape and charge distribution of a reference ligand guide the initial placement of the docking molecule and an interaction energy-based global minimization follows. This hybrid docking was evaluated with soft-core and force field potentials taking into account ligand pose and scoring. Our approach was found to be competitive to a purely receptor-based dock resulting in improved logAUC values when evaluated with DUD and DUD-E. Furthermore, the smoothed potential as evaluated here, was not advantageous when ligand binding poses were compared to experimentally determined conformations. In conclusion we show that a combination of ligand- and receptor-based strategy docking with a force field energy model results in good reproduction of binding poses and enrichment of active molecules against decoys. This strategy is implemented in our tool, LiBELa, available to the scientific community.