A preliminary survey of the peptoid folding landscape.
We present an analysis of the conformational preferences of N-substituted glycine peptoid oligomers. We survey the backbone conformations observed in experimentally determined peptoid structures and provide a comparison with high-level quantum mechanics calculations of short peptoid oligomers. The dominant sources of structural variation derive from: side-chain dependent cis/trans isomerization of backbone amide bonds, side chain stereochemistry, and flexibility in the psi dihedral angle. We find good agreement between the clustering of experimentally determined peptoid torsion angles and local torsional minima predicted by theory for a disarcosine model. The calculations describe a well-defined conformational map featuring distinct energy minima. The general features of the peptoid backbone conformational landscape are consistent across a range of N-alkyl glycine side chains. Alteration of side chain types, however, creates subtle but potentially significant variations in local folding propensities. We identify a limited number of low energy local conformations, which may be preferentially favored by incorporation of particular monomer units. Greater variation in backbone dihedral angles are accessible in peptoids featuring trans amide bond geometries. These results confirm that computational approaches can play a valuable role in guiding the design of complex peptoid architectures and may lead to strategies for introducing constraints that select among a limited number of low energy local conformations.
Butterfoss
Glenn L
GL
Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA. gb77@nyu.edu
Renfrew
P Douglas
PD
Kuhlman
Brian
B
Kirshenbaum
Kent
K
Bonneau
Richard
R
D008956:Models, Chemical; D034442:N-substituted Glycines / Q000737:chemistry*; D017510:Protein Folding
D034442:N-substituted Glycines