Huang, Po-Ssu and Love, John J. and Mayo, Stephen L. (2005) Adaptation of a fast Fourier transform-based docking algorithm for protein design. Journal of Computational Chemistry, 26 (12). pp. 1222-1232. ISSN 0192-8651 http://resolver.caltech.edu/CaltechAUTHORS:20111004-074354772
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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 ~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 Å C_α 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.
|Additional Information:||© 2005 Wiley Periodicals, Inc. Received 29 January 2005; Accepted 8 April 2005. Article first published online: 16 Jun. 2005. Contract/grant sponsor: Howard Hughes Medical Institute. Contract/grant sponsor: Defense Advanced Research Projects Agency. Contract/grant sponsor: Ralph M. Parsons Foundation. Contract/grant sponsor: IBM Shared University Research Grant. Contract/grant sponsor: Army Research Office/Institute for Collaborative Technologies. The authors would like to thank Marie Ary, Christina L. Vizcarra, and Benjamin D. Allen for editing and reviewing the manuscript.|
|Subject Keywords:||Algorithms; Models: Molecular; Crystallography: X-Ray; Protein Conformation; Proteins; Fourier Analysis; protein docking; protein design; reduced side-chain representation; homodimer; FFT; de novo dimer generation|
|Official Citation:||Huang, P.-S., Love, J. J. and Mayo, S. L. (2005), Adaptation of a fast Fourier transform-based docking algorithm for protein design. Journal of Computational Chemistry, 26: 1222–1232. doi: 10.1002/jcc.20252|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||04 Oct 2011 15:07|
|Last Modified:||04 Oct 2011 15:07|
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