Fragment-Based Ligand-Protein Contact Statistics: Application to Docking Simulations

In this work, the information contained in the contacts between fragments of small-molecule ligands and protein residues has been collected and its exploitability has been verified by using the scoring of docking simulations as a test case for bringing about a proof of concept. Contact statistics between small-molecule fragments and binding site residues were collected and analyzed using a dataset composed of 200,000+ binding sites and associated ligands, derived from the database of the LIBRA ligand binding site recognition software, as a starting point. The fragments were generated by applying the decomposition algorithm implemented in BRICS. A simple “potential” based on the contact frequencies was tested against the CASF-2013 benchmark; its performance was then evaluated through the rescoring of docking poses generated for the DUD-E dataset. The results obtained indicate that this approach, its simplicity notwithstanding, yields promising results that are comparable, and in some cases, superior, to those obtained with other, more complex scoring functions.