Evolutionary Pareto-optimization of stably folding peptides

Background: As a rule, peptides are more flexible and unstructured than proteins with their substantial stabilizing hydrophobic cores. Nevertheless, a few stably folding peptides have been discovered. This raises the question whether there may be more such peptides that are unknown as yet. These molecules could be helpful in basic research and medicine. Results: As a method to explore the space of conformationally stable peptides, we have developed an evolutionary algorithm that allows optimization of sequences with respect to several criteria simultaneously, for instance stability, accessibility of arbitrary parts of the peptide, etc. In a proofof-concept experiment we have perturbed the sequence of the peptide Villin Headpiece, known to be stable in vitro. Starting from the perturbed sequence we applied our algorithm to optimize peptide stability and accessibility of a loop. Unexpectedly, two clusters of sequences were generated in this way that, according to our criteria, should fo...

• Type: Journal
• Year: 2008
• Where: BMCBI
• Authors: Wolfram Gronwald, Tim Hohm, Daniel Hoffmann
• Keywords: BMCBI 2008, Peptides, Stable Peptides, Villin Headpiece