PNNL

Abstract

Titania (TiO2) is used extensively in biomedical applications; efforts to boost the biocompatibility of TiO2 include coating it with the titania binding hexamer, RKLPDA. To understand the binding mechanism of this peptide, we employ molecular dynamics simulations enhanced by metadynamics to study three amino acids present in the peptide—arginine (R), lysine (K), and aspartate (D), on four TiO2 variants that have different degrees of surface hydroxyl groups. We find that binding is a function of both sidechain charge and structure, with R binding to all four surfaces, whereas the affinity of K and D is dependent on the distribution of hydroxyl groups. Informed by this, we study the binding of the titania binding hexamer and dodecamer (RKLPDAPGMHTW) on two of the four surfaces, and we see strong correlations between the binding free energy and the primary binding residues, in agreement with prior experiments and simulations. We propose that the discrepancies observed in prior work stem from distribution of surface hydroxyl groups that may be difficult to precisely control on the TiO2 interface. The studies of amino acid binding on all four variants of titania to probe the effects of surface charge state and hydroxyl coverage, and binding of the 6mer and 12mer aptamers on the neutral hydroxylated surface were supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, as part of the Energy Frontier Research Centers program: CSSAS, The Center for the Science of Synthesis Across Scales under Award Number DE-SC0019288. The study of 6mer and 12mer aptamer binding on the negative non hydroxylated surface was supported by National Institute of Health award R21 A126113. This work was facilitated using computational, storage, and networking infrastructure provided by the Hyak supercomputer system, supported in part by the University of Washington and NSF MRI program CHE-1624430. The Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.