Peptoids are N-substituted oligoglycines and can fold into well-defined 3D motifs that mimic peptide secondary structure. Owing to the lack of backbone amide hydrogens, both cis- and trans- amide ω-angle conformations are viable. Simulations of (S)-N-(1-phenylethyl) glycine (SPE) multimers with the General Amber Force Field (gaff) show an incorrect phi angle preference that does not match known NMR structures. Implementing modified parameters for the backbone φ-angle (gaff+phi) corrects this preference as observed in microsecond long REMD simulations in implicit solvent and results in stable folded cis-amide helical structures. Simulations for other oligomers with bulky chiral sidechains such as naptoid (1-phenylethyl) and other ordered oligomers highlight additional applicability of these backbone parameters. Interestingly, these modified φ-angle parameters naturally induce cis ω-angle populations necessary for helix formation and produce cis-trans ratios that match experiment. This helical propensity increases steadily with chain length, hinting at folding cooperativity and decreases with rising temperature until a clear melting transition is observed. BICePs, a Bayesian inference method for comparing conformational populations from computational simulations and sparse experimental observables (such as a limited number of NOE distance restraints from 2D NMR spectroscopy) shows improved agreement with experiment for the gaff+phi parameters.   <br/>

Improved prediction of peptoid structure and dynamics

250th National Meeting (2015)

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