title: Protein docking using spherical polar Fourier correlations.
abstract: We present a new computational method of docking pairs of proteins by using spherical polar Fourier correlations to accelerate the search for candidate low-energy conformations. Interaction energies are estimated using a hydrophobic excluded volume model derived from the notion of "overlapping surface skins," augmented by a rigorous but "soft" model of electrostatic complementarity. This approach has several advantages over former three-dimensional grid-based fast Fourier transform (FFT) docking correlation methods even though there is no analogue to the FFT in a spherical polar representation. For example, a complete search over all six rigid-body degrees of freedom can be performed by rotating and translating only the initial expansion coefficients, many unfeasible orientations may be eliminated rapidly using only low-resolution terms, and the correlations are easily localized around known binding epitopes when this knowledge is available. Typical execution times on a single processor workstation range from 2 hours for a global search (5 x 10(8) trial orientations) to a few minutes for a local search (over 6 x 10(7) orientations). The method is illustrated with several domain dimer and enzyme-inhibitor complexes and 20 large antibody-antigen complexes, using both the bound and (when available) unbound subunits. The correct conformation of the complex is frequently identified when docking bound subunits, and a good docking orientation is ranked within the top 20 in 11 out of 18 cases when starting from unbound subunits. Proteins 2000;39:178-194.
authors.affiliation: Department of Computing Science, King's College, University of Aberdeen, Aberdeen, United Kingdom. dritchie@csd.abdn.ac.uk
authors.forename: D W
authors.initials: DW
authors.lastname: Ritchie
authors.forename: G J
authors.initials: GJ
authors.lastname: Kemp
mesh_terms: D000465:Algorithms; D000818:Animals; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013997:Time Factors
chemical_list: D000936:Antigen-Antibody Complex; D004791:Enzyme Inhibitors; D004798:Enzymes