title: Q-Dock: Low-resolution flexible ligand docking with pocket-specific threading restraints.
abstract: The rapidly growing number of theoretically predicted protein structures requires robust methods that can utilize low-quality receptor structures as targets for ligand docking. Typically, docking accuracy falls off dramatically when apo or modeled receptors are used in docking experiments. Low-resolution ligand docking techniques have been developed to deal with structural inaccuracies in predicted receptor models. In this spirit, we describe the development and optimization of a knowledge-based potential implemented in Q-Dock, a low-resolution flexible ligand docking approach. Self-docking experiments using crystal structures reveals satisfactory accuracy, comparable with all-atom docking. All-atom models reconstructed from Q-Dock's low-resolution models can be further refined by even a simple all-atom energy minimization. In decoy-docking against distorted receptor models with a root-mean-square deviation, RMSD, from native of approximately 3 A, Q-Dock recovers on average 15-20% more specific contacts and 25-35% more binding residues than all-atom methods. To further improve docking accuracy against low-quality protein models, we propose a pocket-specific protein-ligand interaction potential derived from weakly homologous threading holo-templates. The success rate of Q-Dock employing a pocket-specific potential is 6.3 times higher than that previously reported for the Dolores method, another low-resolution docking approach.
authors.affiliation: Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street NW, Atlanta, Georgia 30318, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Brylinski
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D008024:Ligands; D008956:Models, Chemical; D011506:Proteins / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry; D012984:Software; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D011956:Receptors, Cell Surface