Simulation of the Co-assembly of Peptide Amphiphiles and Sugar-based Hydrogelators

Peptide amphiphiles (PAs) are molecules consisting of a hydrophobic alkyl tail, an amino acid hydrophobic peptide block, and a bioactive polar epitope head group. When the peptide sequence includes amino acids with a high beta-sheet formation propensity, long cylindrical nanofibers are observed. PA molecule self-assembly is driven mostly by the interplay of hydrogen bonding and hydrophobic forces over a wide range of length scale. This self-assembling property shows great promise in the development of novel materials and can greatly expand the structural and functional space of supramolecular nanostructures. Though hydrogen bonds clearly play a key role in the formation of high-aspect-ratio fibers, the self-assembly process is not fully understood. This research focused on exploiting the role of molecular interactions in PAs’ self- and co-assembly with the low molecular weight gelator DBSCOOH using computational tools such as dynamic molecular simulation. Various properties were calculated to illustrate the interactions that govern the self- and co-assembly of the examined compounds. The results of the simulation indicate that intermolecular H-bond interactions are formed between the PA and DBSCOOH. Whereas intermolecular H-bonds between PA molecules are not affected by the presence of DBSCOOH, intermolecular H-bonds between DBSCOOH molecules are affected by the presence of the PA. This appears to signal that PAs undergo self-sorting, a conclusion that is supported by experimental data. The peptide presence causes DBSCOOH to alter its assembly fashion by increasing the intramolecular interactions. This may lead to a more rigid structure of the DBSCOOH molecule. DBSCOOH acts as an additive adsorbed onto the PA nanofibers. The supramolecular interactions between the PA and DBSCOOH facilitate interfacial interactions, which results in improved bulk properties.