Characterizing the Conformer Dependence on the Self-Assembly of Diphenylalanine

Diphenylalanine (FF) self-assembles into highly ordered and remarkably stable nanotubes which have a wide variety of potential biomaterial applications. Explicating the FF self-assembly mechanism would enable the rational design of a FF-based biomaterial. Utilizing all-atom molecular dynamics, we demonstrate that dispersed FF monomers initially aggregate into a disordered aggregate by means of backbone–backbone interactions. Results from quantum mechanical calculations suggest the individual monomers within this FF aggregate then undergo a large structural reorientation into conformers with higher internal energies. Although in a less stable conformation, the dihedral space of this conformer allows for further hydrophobic packing. Steric sidechain size and phenyl–backbone interactions are the source of the energetic barrier between conformers, suggesting modification resulting in increased rigidity of the dihedral state would alter the ordering in FF self-assembly.