Despite the widespread utilization of bio-titania interfaces, such as in biomedical implants, drug delivery and biosensors, biomolecular recognition and interactions at these interfaces remain far from being understood. Predicting and controlling bio-interfacial properties is extremely challenging without a molecular-level comprehension of how biomolecules interact with material surfaces and the factors that influence these interactions. We utilize cutting-edge techniques such as Replica Exchange with Solute Tempering (REST) and Metadynamics to study, at the negatively-charged aqueous rutile TiO2 (110) surface, the adsorption of a number of amino acids and titania-binding peptides and calculate their binding free energies.
This is performed by studying analogues of six amino acids (Ala, Arg, Asp, Lys, Phe, and Ser) and two experimentally-identified titania binding peptides, namely Ti1 (QPYLFATDSLIK) and Ti2 (GHTHYHAVRTQT). Our results revealed a stronger affinity between charged amino acids and the titania surface compared to uncharged amino acids. In addition, peptides Ti1 and Ti2 were found to have a similar binding free energy but different binding mechanisms. While Ti2 revealed an enthalpic binding, Ti1 showed an entropic binding mechanism. The concept of enthalpically- and entropically-driven peptide binding was recently proposed for the adsorption of peptides onto gold surfaces. The contribution of each residue to binding to the titania surface was evaluated in both peptides. Finally, the effect of using Ca2+ counterions on the adsorption of both peptides to titania was studied. Our results provide valuable insights into the complex interplay between peptide sequence, structure, and binding at the aqueous titania interface.