Molecular dynamics simulations of interplay between RGD and rutile surfaces with designed topographies

The Arg-Gly-Asp sequence (RGD), a ubiquitous adhesive motif in extracellular matrix proteins, exhibits a high affinity to the predominant osteoblast integrin; thus it has been regarded as a promising candidate for biomimic coating to emulate biology in the fabrication of bone-anchored implant surfaces, especially the widely used titanium-based materials. The present study aims to explore the molecular scale events that occur when RGD is placed close to the rutile TiO₂ (110) surface by employing classical all-atom molecular dynamics simulations. Local grooves with different depths were introduced in the substrate surfaces to figure out the effect of surface topography on the binding modes of RGD with rutile. The simulation results show that the negatively charged carboxyl groups of RGD are able to break through the barriers from surface hydrations, forming direct bonds with the surface Ti atoms. However, this occurs on the premise that an anchoring site on the rutile surface has been provided to the peptide with an external intervention. Since the unsaturated atoms on the top-layer of groove walls seem to be underlying active sites for peptide adsorption, the presence of surface grooves will largely affect the RGD-rutile binding modes. If RGD can be locked on the bottom of groove via the direct bonds between carboxyl groups and surface Ti atoms, the positively charged groups (guanidine or amino group) are inclined to form hydrogen bonds with surface O atoms on the groove walls, when the length of the rest chain allows. However, once RGD is connected to the bottom of groove with both Arg and Asp side chains "trapped" in a "horseshoe" configuration, the formation of hydrogen bonds between the peptide and the groove walls will be greatly suppressed. The results also indicate that the dominant factors determining the binding strength of RGD-rutile complex are the concrete types of interaction and the number of jointing points. It is anticipated that the findings presented here will ultimately contribute to the biomimetic modification of implants, by suggesting how to tailor the surface topography of implants to induce the desirable biological function.