De novo structure prediction and experimental characterization of folded peptoid oligomers

Glenn L. Butterfoss, Barney Yoo, Jonathan N. Jaworski, Ilya Chorny, Ken A. Dill, Ronald N. Zuckermann, Richard Bonneau, Kent Kirshenbaum, Vincent A. Voelz

Research output: Contribution to journalArticlepeer-review


Peptoid molecules are biomimetic oligomers that can fold into unique three-dimensional structures. As part of an effort to advance computational design of folded oligomers, we present blind-structure predictions for three peptoid sequences using a combination of Replica Exchange Molecular Dynamics (REMD) simulation and Quantum Mechanical refinement. We correctly predicted the structure of a N-aryl peptoid trimer to within 0.2 Å rmsd-backbone and a cyclic peptoid nonamer to an accuracy of 1.0 Å rmsd-backbone. X-ray crystallographic structures are presented for a linear N-alkyl peptoid trimer and for the cyclic peptoid nonamer. The peptoid macrocycle structure features a combination of cis and trans backbone amides, significant nonplanarity of the amide bonds, and a unique "basket" arrangement of (S)-N (1-phenylethyl) side chains encompassing a bound ethanol molecule. REMD simulations of the peptoid trimers reveal that well folded peptoids can exhibit funnel-like conformational free energy landscapes similar to those for ordered polypeptides. These results indicate that physical modeling can successfully perform de novo structure prediction for small peptoid molecules.

Original languageEnglish (US)
Pages (from-to)14320-14325
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number36
StatePublished - Sep 4 2012


  • Foldamer
  • Molecular simulation.

ASJC Scopus subject areas

  • General


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