A Tail of Two Peptide Amphiphiles: Effect of Conjugationwith Hydrophobic Polymer on Folding of Peptide Sequences.

Peptide amphiphiles (PA) offer thepotential of incorporating biologicalfunction into synthetic materials for tissue engineering in regenerativemedicine. These hybrid conjugates are known to undergo self-assemblystarting from single molecules to nanofibers before turning into hydrogelscaffoldssuch a process involves conformational changes insecondary structures of peptides. Therefore, insights on the abilityof peptide amphiphiles to form secondary structure as single moleculesare useful for understanding self-assembly behavior. We report herea molecular simulation study of peptide folding by two PA sequences,each contains an alkyl tail and short peptide segment. The alkyl tailis observed to play two opposing roles in modulating sequence-dependentfolding kinetics and thermodynamics. On one hand, it restricts conformationalfreedom reducing the entropic cost of folding, which is thus promoted.On the other hand, it acts as an interaction site with nonpolar peptideresidues, blocking the peptide from helix nucleation, which reducesfolding. [ABSTRACT FROM AUTHOR]