title: Design of MHC I stabilizing peptides by agent-based exploration of sequence space.
abstract: 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-2K(b). 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-2K(b) 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.
authors.affiliation: Center for Membrane Proteomics, Institute of Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe-Universität, Siesmayerstr. 70, D-60323 Frankfurt am Main, Germany. hiss@bioinformatik.uni-frankfurt.de
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.forename: Anne
authors.initials: A
authors.lastname: Bredenbeck
authors.forename: Florian O
authors.initials: FO
authors.lastname: Losch
authors.forename: Paul
authors.initials: P
authors.lastname: Wrede
authors.forename: Peter
authors.initials: P
authors.lastname: Walden
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D008962:Models, Theoretical; D016571:Neural Networks, Computer; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D015202:Protein Engineering
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides