title: A scoring function for docking ligands to low-resolution protein structures.
abstract: We present a docking method that uses a scoring function for protein-ligand docking that is designed to maximize the docking success rate for low-resolution protein structures. We find that the resulting scoring function parameters are very different depending on whether they were optimized for high- or low-resolution protein structures. We show that this docking method can be successfully applied to predict the ligand-binding site of low-resolution structures. For a set of 25 protein-ligand complexes, in 76% of the cases, more than 50% of ligand-contacting residues are correctly predicted (using receptor crystal structures where the binding site is unspecified). Using decoys of the receptor structures having a 4 A RMSD from the native structure, for the same set of complexes, in 72% of the cases, we obtain at least one correctly predicted ligand-contacting residue. Furthermore, using an 81-protein-ligand set described by Jain, in 76 (93.8%) cases, the algorithm correctly predicts more than 50% of the ligand-contacting residues when native protein structures are used. Using 3 A RMSD from native decoys, in all but two cases (97.5%), the algorithm predicts at least one ligand-binding residue correctly. Finally, compared to the previously published Dolores method, for 298 protein-ligand pairs, the number of cases in which at least half of the specific contacts are correctly predicted is more than four times greater.
authors.affiliation: Center of Excellence in Bioinformatics, University at Buffalo, 901 Washington St., Buffalo, New York 14203, USA.
authors.forename: Eckart
authors.initials: E
authors.lastname: Bindewald
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D055672:Static Electricity
chemical_list: D008024:Ligands