Atomistic Pictures of Self-Assembled Helical Peptide Nanofibers

Spontaneous self-assembly of peptides has been at the forefront of supramolecular chemistry and materials science research over the last two decades. Despite the wealth of information on the morphology of the assembled objects, atomic resolution details of molecular arrangements inside them are largely unknown. In this paper, we investigated non-covalent assemblies of zwitterionic l-phenylalanine tripeptides in water using all-atom explicit-solvent molecular dynamics computer simulations. Our studies produced atomistic pictures of spontaneously assembled nanofibers composed of hundreds of peptide molecules. The dimensions of the nanofibers varied from 10 to 18 nm, with irregular helical twists along the long axes. Previously published experimental data, acquired under similar conditions, provided direct validation of the fibrous morphology and indirect support for the non-trivial helicity observed in our simulations. Quantitative analyses of peptide-water and peptide-peptide interactions revealed heterogeneous local environments of molecules across the nanometer length scales. The combination of electrostatic, hydrogen bonding, van der Waals, and hydrophobic interactions, adopted by a single molecule, was dependent on its relative position inside the fiber. Despite the presence of three hydrophobic phenyl groups, very few molecules were found to be completely shielded from the surrounding water, indicating a subtle role of the hydrophobic effect. Limited conformational flexibility of the tripeptide, along with bare electrostatic interactions, appeared to play a crucial role in the emergence of fibrous morphology of the nanostructures. Our analyses led us to formulate plausible qualitative explanations of the assembly behavior in terms of thermodynamic driving forces and kinetic considerations. We established a clear relationship between details of chemical interactions operating within few molecules and characteristics of the self-assembled states at much longer length scales.