Steered molecular dynamics studies of the potential of mean force for peptide amphiphile self-assembly into cylindrical nanofibers

Steered molecular dynamics (SMD) simulations were applied to determine the potential of mean force for the self-assembly of peptide amphiphile (PA) nanofibers, specifically considering a single PA adding to a growing cylindrical nanofiber at 310 K. It is found that the free energy, enthalpy, and entropy differences for this assembly process are -67 kcal/mol, -71.5 kcal/ml, and -14.5 cal/(mol K), respectively, and therefore that enthalpy provides the driving force for self-assembly to form a fiber. A pairwise interaction analysis shows that both electrostatic and van der Waals interactions play important roles in the self-assembly process, with the van der Waals interaction being the larger effect. The mechanistic picture that emerges from this work is that as the PA is pulled from the fiber, the interaction evolves through three stages: (1) initially electrostatic interactions between the charged head of the pulled PA and other PAs, and between the pulled PA and solvent are dominant, (2) after the charged head emerges, the rest of the peptide comes out, with both PA-solvent electrostatic interactions and van der Waals interactions being significant, and (3) in the last step, the alkane tail emerges, dominated by van der Waals interactions with either peptide or solvent.