A new design and computational survey on RGD biofunctionalized RADA16-I self-assembling peptide for tissue...

Tissue engineering constantly needs innovative and biocompatible materials, and peptide-based materials seem very inspiring. Here we developed two new self-assembling peptides based on RADA16-I and RGD peptides and studied their potential in forming nanofibers under various conditions using all-atom and coarse-grained molecular dynamics simulation methods. First, a double-tailed RGD (dtRGD) peptide was designed by attaching two RADA16-I tails to an RGD-containing loop in which two disulfide bonds stabilized the loop integrity. In the second design, we bonded one side of the loop to the DA16-I tail (otRGD). The dtRGD peptides exhibited a remarkable propensity to form beta-sheet structures during all-atom MD simulations, starting from the initial random coil structure. The most promising outcomes in nanofiber formation were observed when simulating these peptides in a salt concentration that mimics the extracellular matrix. The representation of the RGD epitope was also significantly evident under these conditions. In the otRGD design, the final structure displayed a globular-like morphology, predominantly possessing coils and alpha-helices secondary structures, while maintaining effective RGD peptide exposure. This investigation signified the possibility of a new RGD representing biomaterial for tissue engineering purposes, however, further theoretical and experimental investigations are imperative to unlock their capabilities and applications.