Skip Navigation


PEDS Advance Access originally published online on February 21, 2007
Protein Engineering Design and Selection 2007 20(3):99-108; doi:10.1093/protein/gzl054
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
20/3/99    most recent
gzl054v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hiss, J. A.
Right arrow Articles by Schneider, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hiss, J. A.
Right arrow Articles by Schneider, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Design of MHC I stabilizing peptides by agent-based exploration of sequence space

Jan A. Hiss1,5, Anne Bredenbeck2,3, Florian O. Losch2, Paul Wrede4, Peter Walden2 and Gisbert Schneider1

1 Center for Membrane Proteomics, Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-Universität, and Institute of Cell Biology and Neuroscience, Siesmayerstr. 70, D-60323 Frankfurt am Main, Germany 2 Department of Dermatology, Clinical Research Group Tumor Immunology, Charité–Universitätsmedizin Berlin, Schumannstr. 20/21, D-10117 Berlin, Germany 3 Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany 4 Institute for Molecular Biology and Bioinformatics, Charité–Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195 Berlin, Germany

5 To whom correspondence should be addressed. E-mail: hiss{at}bioinformatik.uni-frankfurt.de

Identification of molecular features that determine peptide interaction with major histocompatibility complex I (MHC I) is essential for vaccine development. We have developed a concept for peptide design by combining an agent-based artificial ant system with artificial neural networks. A jury of feedforward networks classifies octapeptides that are recognized by mouse MHC I protein H-2Kb. Prediction accuracy yielded a correlation coefficient of 0.94. Peptides were designed in machina by the artificial ant system and tested in vitro for their MHC I stabilizing effect. The behavior of the search agents during the design process was controlled by the jury network. The experimentally determined prediction accuracy was 89% for the designed stabilizing and 95% for the non-stabilizing peptides. Novel H-2Kb stabilizing peptides were conceived that reveal extensions of known residue motifs. The combined network-agent system recognized context dependencies of residue positions. A diverse set of novel sequences exhibiting substantial activity was generated.

Keywords: ant colony optimization/artifical neural networks/MHC I/peptide design

Received August 10, 2006; revised November 24, 2006; accepted November 25, 2006.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.