9513250 Evans Within biomineralized structures, there exists a group of macromolecules whose primary function is the nucleation of inorganic crystals and the regulation of their growth. These molecules are referred to as "acidic" template macromolecules. According to the paradigm of molecular complementarity, an effective template macromolecule must organize its ligand atoms in a compact array, such that this array complements the corresponding metal atom array on a crystal motif (Mann, 1993). The question is, how is this "organization" of the template macromolecule achieved? In the case of protein template macromolecules, such as the "acidic" proteins found in mollusc shell, tooth dentine, and bone, the problem of attaining this organization becomes a problem in protein folding. Hence, if we can determine how "acidic" proteins fold in the presence of divalent cations and/or mineral crystal surfaces, we can (1) learn how these complex proteins work, and (2) eventually apply this information towards the design of inorganic motif-recognition polymers that can be utilized as components in the fabrication of novel composite materials. Based on pioneering NMR protein-folding studies of an "acidic" template phosphoprotein, phosphophoryn, I have determined that an "acidic" template protein undergoes pH- and cation-induced global folding transitions, and that these folding transitions are mediated by hinge or intervening domains that are flanked on either side by the metal-binding polyelectrolyte domains. I hypothesize that this hinge-mediated folding process may represent a possible mechanism for creating organized template molecular surfaces that will complement certain crystal motifs. In this CAREER research proposal, I will refine our knowledge of the polyelectrolyte-hinge folding process by using the following strategy: Explore hinge function the cation-induced folding process by utilizing synthetic polyelectrolyte-hinge-polyelectrolyte (PHP) peptidomimetics, NMR spectroscopy, and mo lecular modeling. %%% Biomineralized tissues, such as bone, teeth, sea shells, and plankton, represent a naturally-occuring composite material: Proteins and polysaccharides combine with inorganic mineral crystals to form highly structured, well-defined materials which have existed for millions of years. Can we, as scientists, learn anything about these structures that might help us in our quest for new bio- and eco-compatible materials? The answer is yes, since we are now beginning to understand that certain proteins can bind to minerals via a specific folding pathway, which, in turn, can affect the dimension and size of mineral crystals on a microscopic level. This proposal plans to study the amino acid sequences of certain biomineralization proteins, and, determine how metal ions affect the shape or "folding" of the protein. Our methods will include nuclear magnetic resonance spectroscopy and computer modeling. This information will give us some idea of how the proteins themselves regulate the formation of mineral crystal sizes, and ultimately, the formation of composite structures. My teaching proposal will emphasize teacher-student programs which will help to change the learning process at the undergraduate and graduate level at NYU, and, prepare high school and elementary school students for what science skills they will need to develop in their college years. ***
