Globular proteins commonly use structural metals to promote folding and enhance stability. There are no good examples of similar metal utilization in fibrillar proteins such as collagen. We hypothesized a metal binding site at the end of an A:B:C-type collagen triple helix could be designed to enhance folding and stability without compromising specificity. A heterospecific metal binding site was computationally designed by sampling backbone and sidechain conformations of C-terminal amino acids of the triple helix to optimize metal site geometry. Experimental characterization of the designed sequences confirms that zinc-binding enhances structure and thermal stability of the A:B:C heterotrimer peptides under physiological buffer conditions. By varying metal concentration, it is possible to study the relative contributions of electrostatic interactions and metal binding, to triple helix stability and structure. Metal-directed switching of triple helical structure has potential applications in self-assembly of higher order biomaterials, translational regenerative medicine and drug design.View Large Image | View Hi-Res Image | Download PowerPoint Slide