In silico characterization of protein chimeras: Relating sequence and function within the same fold

Buske, Fabian A., Their, Ricarda, Gillam, Elizabeth M. J. and Boden, Mikael (2009) In silico characterization of protein chimeras: Relating sequence and function within the same fold. Proteins: Structure, Function, and Bioinformatics, 77 1: 111-120. doi:10.1002/prot.22422


Author Buske, Fabian A.
Their, Ricarda
Gillam, Elizabeth M. J.
Boden, Mikael
Title In silico characterization of protein chimeras: Relating sequence and function within the same fold
Journal name Proteins: Structure, Function, and Bioinformatics   Check publisher's open access policy
ISSN 0887-3585
Publication date 2009-10-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/prot.22422
Volume 77
Issue 1
Start page 111
End page 120
Total pages 109
Editor E. E. Lattman
Place of publication United States
Publisher John Wiley & Sons, Inc.
Collection year 2010
Language eng
Subject C1
060107 Enzymes
970106 Expanding Knowledge in the Biological Sciences
060102 Bioinformatics
Abstract The exploration of novel proteins via recombination of fragments derived from structurally homologous proteins has enormous potential for medicine and biotechnology. This modular exchange of sequence material puts novel activities, substrate specificities, and stability within reach of a semi-random search. This article takes stock of the growing resource of experimentally characterized chimeric proteins within a homologous protein family to build sequence-function models that can effectively guide the construction of new libraries. A novel framework for predicting structural viability of chimeric proteins, only assuming knowledge of their sequence and their parental structure, is presented. Removing a major barrier in previous work, the model processes any sequence that derives from parents with similar folds. The method naturally mixes test and training data from site-directed recombination, DNA shuffling, or random mutagenesis experiments. We train a model from a site-directed recombination library with state-of-the-art prediction accuracy on hold-out test data from the same experimental source and convincing performance on chimeras with a different origin. Specifically, the model is used to assess the structural viability of P450 chimeras deriving from proteins with only 18% sequence similarity to those used for model tuning. Proteins 2009. © 2009 Wiley-Liss, Inc.
Keyword bioinformatics
protein design
DNA shuffling
protein structure
machine learning
kernel method
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 25 Mar 2010, 01:29:09 EST by Timothy Hazelton on behalf of Institute for Molecular Bioscience