De novo structure prediction and experimental characterization of folded peptoid oligomers.
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.
Center for Genomics and Systems Biology, New York University, NY 10003, USA.
Glenn L
GL
Butterfoss
Barney
B
Yoo
Jonathan N
JN
Jaworski
Ilya
I
Chorny
Ken A
KA
Dill
Ronald N
RN
Zuckermann
Richard
R
Bonneau
Kent
K
Kirshenbaum
Vincent A
VA
Voelz
D018360:Crystallography, X-Ray; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D034444:Peptoids / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding
D034444:Peptoids; D011108:Polymers