Nature relies on the remarkable folding properties of proteins and nucleic acids to perform vital chemical work. Not surprisingly, synthetic chemists have long set their sights on developing non-natural molecules—called “foldamers”—that can harness similar folding properties for a number of diverse applications including nanomaterials, biotherapeutics, and chemical catalysts.
Peptoids (N-substituted oligoglycines) are bio-inspired synthetic heteropolymers that can fold into a number of diverse structural scaffolds. In a new paper by Mukherjee et al., we report on improved simulation potentials that better model peptoid helices, a key motif for peptide mimics. We then use a statistical mechanical helix-coil model to examine the thermodynamic forces that drive helix formation. We find that, unlike peptides, peptoid helices can increase their entropy upon folding, indicating that steric bulk of plays a large role in stabilizing helices. These findings will help future efforts in computational peptoid design.
Just Accepted manuscript: http://dx.doi.org/10.1021/acs.jpcb.5b09625