Atomistic Pictures of Self-Assembled Helical Peptide\nNanofibers

Abstract

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