Self-Assembly of beta-Peptides: Insight from the Pair and Many-Body Free Energy of Association

Oligomers of beta-peptides with cyclic residues make very stable helices where the amphiphilicity can be tailored via the sequence. These molecules display large-scale hierarchical self-assembly that is very sensitive to the sequence. For example, the globally amphiphilic (GA) sequence of one molecule, beta Y-(ACHC-ACHC-beta K)(3) (model A), self-assembles into long cylinders, which can display a nematic phase, but the nonglobally amphiphilic (non-GA) sequence does not. Interestingly, for a closely related sequence, beta Y-(ACHC-beta F-beta K)(3) (model B), the opposite is true; that is, the non-GA sequence self-assembles into long hollow cylinders, and the GA sequence does not. In this work, the pair and many-body potential of mean force (PMF) between beta-peptides is studied using computer simulations with explicit and implicit solvent. The PMF studies rationalize the experimentally observed trends. In particular, for the sequences that form hollow cylinders, the most stable configuration of a pair of molecules is when they are side-to-side and parallel. The two sequences that do make cylinders have side-to-side parallel configurations with a slight curvature at the minimum in the triplet PMF. The implicit solvent simulations are in qualitative accord with explicit solvent simulations for the pair PMF, suggesting that one could use multibody PMF studies with implicit solvent models to provide insight into the self-assembly of complex molecules.