Superstar: improved knowledge-based interaction fields for protein binding sites

SuperStar is an empirical method for identifying interaction sites in proteins, based entirely on experimental information about non-bonded interactions occurring in small-molecule crystal structures, taken from the IsoStar database. We describe recent modifications and additions to SuperStar, validating the results on a test set of 122 X-ray structures of protein-ligand complexes. In this validation, propensity maps are generated for all the binding sites of these proteins, using four different probes: a charged NH3+ nitrogen atom, a carbonyl oxygen atom, a hydroxyl oxygen atom and a methyl carbon atom. Next, the maps are compared with the experimentally observed positions of ligand atoms of these types. A peak-searching algorithm is introduced that highlights potential interaction hot spots. For the three hydrogen-bonding probes - NH3+ nitrogen atom, carbonyl oxygen atom and hydroxyl oxygen atom - the average distance from the ligand atom to the nearest SuperStar peak is 1.0–1.2 Å (0.8–1.0 Å for solvent-inaccessible ligand atoms). For the methyl carbon atom probe, this distance is about 1.5 Å, probably because interactions to methyl groups are much less directional.