Adsorption of Arginine-Glycine-Aspartate Tripeptide onto Negatively Charged Rutile (110) Mediated by Cations: The Effect of Surface Hydroxylation

Classical molecular dynamics (MD) simulations were employed to investigate the adsorption behaviors of arginine-glycine-aspartate (RGD) tripeptide onto the negatively charged hydroxylated/nonhydroxylated rutile (110) surfaces, mediated by biologically important cations (Na⁺ or Ca²⁺). The simulation results indicate that the inherent nature of the cation determines its binding strength, thereby regulating the adsorption geometry of the peptide. The sparse hydroxyl groups on the nonhydroxylated rutile diminish the probability of H-bond formation between RGD and the surface, resulting in an early desorption of the peptide even with a mediating Na⁺ ion. In contrast, the negatively charged aspartate (Asp) side chain is bridged to the negatively charged hydroxylated rutile by an inner-sphere Na⁺ ion, in coordination with the Asp-rutile hydrogen bonds at the anchoring sites. The inner- and outer-sphere Ca²⁺ ions are demonstrated to be capable of "trapping" RGD on both hydroxylated and nonhydroxylated rutile, in the absence of hydrogen bonds with the surface. The strongly bound inner-sphere mediating Ca²⁺ ion exerts a "gluing" effect on the Asp side chain, producing a tightly packed RGD-rutile complex, whereas a less localized distribution density of the outer-sphere mediating Ca²⁺ ion results in a higher mobility of the Asp side chain. The intramolecular interaction is suggested to facilitate the structural stability of RGD adsorbed on the negative rutile in a "horseshoe" configuration.