Large scale Full QM-MD investigation of small peptides and insulin adsorption on ideal and defective TiO2 (1 0 0) surfaces. Influence of peptide size on interfacial bonds

[Display omitted] •Biomolecule adsorption investigated by Molecular Dynamics/Full Quantum Mechanics method.•Interfacial bonds can then be truly described for the surface adsorption site and molecular groups.•Both surface and adsorbate atomic and electronic structures can be described.•The influence of surface defects and polypeptide structures on the final adsorption state can be highlighted. Large biomolecule interaction with oxide surface has attracted a lot of attention because it drives behavior of implanted devices in the living body. To investigate the role of TiO2 surface structure on a large polypeptide (insulin) adsorption, we use a homemade mixed Molecular Dynamics-Full large scale Quantum Mechanics code. A specific re-parameterized (Ti) and globally convergent NDDO method fitted on high level ab initio method (coupled cluster CCSD(T) and DFT) allows us to safely describe the electronic structure of the whole insulin-TiO2 surface system (up to 4000 atoms). Looking specifically at carboxylate residues, we demonstrate in this work that specific interfacial bonds are obtained from the insulin/TiO2 system that are not observed in the case of smaller peptides (tripeptides, insulin segment chains with different configurations). We also demonstrate that a large part of the adsorption energy is compensated by insulin conformational energy changes and surface defects enhanced this trend. Large slab dimensions allow us to take into account surface defects that are actually beyond ab initio capabilities owing to size effect. These results highlight the influence of the surface structure on the conformation and therefore of the possible inactivity of an adsorbed polypeptides.