(704g) Binding Mechanism of Titania Binding Peptide (TBP) on Titania from MD Simulations

Titanium (Ti) alloys are used in dental and bone implants due to their mechanical strength and biocompatibility. Solid binding peptides have been studied extensively in order to impart bioactive properties to implants, and aid in the process of osseointegration (structural and functional integration of the surface of an external implant with the living bone). In order to boost biocompatibility of Ti implants, titanium binding peptide (TBP), a hexapeptide motif (RKLPDA) that electrostatically binds to Ti surface has been extensively studied, however, the binding mechanism of this peptide is unclear. In this study, we employ molecular dynamics simulations enhanced by replica exchange metadynamics to investigate the binding of TBP on titania. We calculate binding free energy and find that it is in good agreement with experimental dissociation constant. We perform cluster analysis to investigate the different binding poses of TBP on the surface and see that binding occurs through a few conformers. Finally, we compare these structures with that obtained from ssNMR, and find that there is a good match between peptide conformations obtained though experiments and simulations.