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Adaptation of a fast Fourier transform-based docking algorithm for protein design

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. doi:10.1002/jcc.20252.

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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.

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Mayo, Stephen L.0000-0002-9785-5018
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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.
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)UNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
Army Research Office (ARO)UNSPECIFIED
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
Issue or Number:12
Record Number:CaltechAUTHORS:20111004-074354772
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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.
ID Code:25535
Deposited By: Tony Diaz
Deposited On:04 Oct 2011 15:07
Last Modified:09 Nov 2021 16:34

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