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 language||English (US)|
|Number of pages||8|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - May 11 2004|
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