Application of evolutionary algorithm methods to polypeptide folding: comparison with experimental results for unsolvated Ac-(Ala-Gly-Gly)5-LysH+

Martin Damsbo, Brian S Kinnear, Matthew R Hartings, Peder T Ruhoff, Martin F Jarrold, Mark A Ratner

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

We present an evolutionary method for finding the low-energy conformations of polypeptides. The application, called FOLDAWAY,is based on a generic framework and uses several evolutionary operators as well as local optimization to navigate the complex energy landscape of polypeptides. It maintains two complementary representations of the structures and uses the CHARMM force field for evaluating the energies. The method is applied to unsolvated Met-enkephalin and Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+). Unsolvated Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+) has been the object of recent experimental studies using ion mobility measurements. It has a flat energy landscape where helical and globular conformations have similar energies. FOLDAWAY locates several large groups of structures not found in previous molecular dynamics simulations for this peptide, including compact globular conformations, which are probably present in the experiments. However, the relative energies of the different conformations found by FOLDAWAY do not accurately match the relative energies expected from the experimental observations.
Original languageEnglish
JournalProceedings of the National Academy of Science of the United States of America
Volume101
Issue number19
Pages (from-to)7215-7222
Number of pages7
ISSN0027-8424
DOIs
Publication statusPublished - 11. May 2004

Keywords

  • Algorithms
  • Evolution, Molecular
  • Peptides
  • Protein Folding

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