title: Adaptation of a fast Fourier transform-based docking algorithm for protein design.
abstract: Designing proteins with novel protein/protein binding properties can be achieved by combining the tools that have been developed independently for protein docking and protein design. We describe here the sequence-independent generation of protein dimer orientations by protein docking for use as scaffolds in protein sequence design algorithms. To dock monomers into sequence-independent dimer conformations, we use a reduced representation in which the side chains are approximated by spheres with atomic radii derived from known C2 symmetry-related homodimers. The interfaces of C2-related homodimers are usually more hydrophobic and protein core-like than the interfaces of heterodimers; we parameterize the radii for docking against this feature to capture and recreate the spatial characteristics of a hydrophobic interface. A fast Fourier transform-based geometric recognition algorithm is used for docking the reduced representation protein models. The resulting docking algorithm successfully predicted the wild-type homodimer orientations in 65 out of 121 dimer test cases. The success rate increases to approximately 70% for the subset of molecules with large surface area burial in the interface relative to their chain length. Forty-five of the predictions exhibited less than 1 A C(alpha) RMSD compared to the native X-ray structures. The reduced protein representation therefore appears to be a reasonable approximation and can be used to position protein backbones in plausible orientations for homodimer design.
authors.affiliation: Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Po-Ssu
authors.initials: PS
authors.lastname: Huang
authors.forename: John J
authors.initials: JJ
authors.lastname: Love
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Mayo
mesh_terms: D000465:Algorithms; D018360:Crystallography, X-Ray; D005583:Fourier Analysis; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins