Polymer Science Faculty Research


Predicting Binding Conformation of Peptide at Hydroxyapatite Interface: Interplay with Biomineral-Peptide Binding Affinity

Document Type

Conference Proceeding

Publication Date

Spring 3-16-2014


Synthetic short-length peptides have potential applications in the field of biomedical diagnostic and treatment of bone and teeth related diseases. Such peptide sequences have been identified through phage display to have high hydroxyapatite (HAP) binding affinity. Understanding the structure and chemistry of these hydroxyapatite-binding peptides, especially at the interface with hydroxyapatite bio-mineral is crucial with respect to the rational design of such peptides in biomedical assay. In the present study, the conformation of a list of hydroxyapatite-binding peptides as a determinant to the binding affinity is predicted ab initio by using bioinformatics approach RosettaSurface. Two classes of binding conformations have been detected, one is alpha-helix with side chain undergoing a spatial registration to hydroxyapatite surface atoms, and the other is random coil with flexible conformation. The binding affinity of both conformations is relied upon the tight electrostatic interaction of positively charged lysine residue to phosphate ions on HAP surface. In order to compare the binding affinity between peptide with helix and random coil conformations, steered molecular dynamics (SMD) is applied to the non-equilibrium desorbing process of peptide from surface. The binding force of peptide to both HAP (100) and (001) faces was measured. It is reflected on SMD simulation that the intrinsic secondary structure of HAP-binding peptide largely affects the binding affinity, presumably through the entropy-enthalpy trading mechanism at the interface. We expect our results could complement current understanding on the hypothesis of flexible polyelectrolyte interacting with charged solid surface.

Publication Title

Abstracts of Papers of the American Chemical Society