title: Docking of small ligands to low-resolution and theoretically predicted receptor structures.
abstract: We have developed a simple docking procedure that is able to utilize low-resolution models of proteins created by structure prediction algorithms such as threading or ab initio folding to predict the conformation of receptor-small ligand complexes. In our approach, using only approximate, discretized models of both molecules, we search for the steric and quasi-chemical complementarity between a ligand and the receptor molecules. This averaging procedure allows for the compensation of numerous structural inaccuracies resulting from the theoretical predictions of the receptor structure. The best relative orientation of these two models is obtained by an exhaustive scan over the rigid body's six-dimensional translational and rotational degrees of freedom. The search method is based on a real space grid-searching algorithm, unlike docking methods based on the fast Fourier Transform algorithm. We have applied this algorithm to rebuild structures of several complexes available in the Protein Data Bank. The structures of the receptors are produced by means of our threading algorithm PROSPECTOR, subsequently refined, and then utilized in the docking experiment. In many cases, not only is the localization of the binding site on the receptor surface correctly identified, but the proper orientation of the bounded ligand is also reasonably well reproduced within the level of accuracy of the modeled receptor itself.
authors.affiliation: Laboratory of Computational Genomics, Donald Danforth Plant Science Center, St. Louis, Missouri 63141, USA.
authors.forename: Marek
authors.initials: M
authors.lastname: Wojciechowski
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Skolnick
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D016208:Databases, Factual; D029968:Escherichia coli Proteins; D008024:Ligands; D046911:Macromolecular Substances; D008956:Models, Chemical; D015394:Molecular Structure; D033902:Periplasmic Binding Proteins; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008024:Ligands; D046911:Macromolecular Substances; C461619:MalE protein, E coli; D033902:Periplasmic Binding Proteins; D011956:Receptors, Cell Surface