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.

二氧化钛（TiO ₂）被广泛用于生物医学领域。增强TiO ₂生物相容性的努力包括用二氧化钛结合六聚体RKLPDA对其进行包被。为了了解该肽的结合机理，我们利用分子动力学模拟（通过元动力学来增强）来研究肽中存在的三种氨基酸（精氨酸（R），赖氨酸（K）和天冬氨酸（D））在四种TiO _2上具有不同程度的表面羟基的变体。我们发现结合是侧链电荷和结构的函数，R结合到所有四个表面，而K和D的亲和力取决于羟基的分布。以此为依据，我们研究了二氧化钛结合六聚体和十二聚体（RKLPDAPGMHTW）在四个表面中的两个表面上的结合，并且与先前的实验和模拟相一致，我们发现结合自由能与主要结合残基之间具有很强的相关性。我们建议，在先前的工作中观察到的差异源于可能难以精确控制TiO ₂界面的表面羟基的分布。