Coarse-Grained Molecular Dynamics Simulations Illustrate the Supramolecular Structures of Co-Assembling Tetrapeptide Motifs Comprising Tyrosine and Phenylalanine

Investigating peptide-based self-organization is central to the emerging field of biologically inspired soft materials. Correspondingly, structural studies of peptide nanomaterials using molecular dynamics simulations have elucidated various pathways for the co-assembly of short peptides, thereby promoting the further development of bioinspired building blocks and informing predictions for the formation of these assemblies at the supramolecular level. In this study, we investigated the assembly processes of tetrapeptide motifs with repeating patterns, such as YFYF and FYFY, which contain tyrosine (Y) and phenylalanine (F), using coarse-grained (CG) molecular dynamics (MD) simulations with these tetrapeptides in water, as well as acetone-water and cyclohexane-water mixtures. The results underscore the key structural features of tetrapeptide-based assemblies and the ways in which their self-organization processes depend on the effective peptide concentrations and varying polarities of the organizing media, owing to the presence of co-solvents, providing insight into the development of co-assembled nanostructures.