The de novo design of molecular switching peptides is of increasing interest because it tests and extends our fundamental understanding of this process while laying the groundwork for the creation of new chemical and biological reagents. Addressing this problem through protein design requires conditional stabilization of the target fold with concomitant destabilization of alternative folds. In the following work, I have exploited properties of the α-helix to design two different classes of helical molecular switching peptides. These peptides undergo structural stabilization upon exposure to the appropriate chemical signal, phosphorylation or metal-binding. Once conformationally stabilized, they can then participate in further biologically relevant activities, oligomerization or membrane lysis. Both sets of switches exhibited successful design of inducible activity. Studying both systems has also contributed to our understanding of determinants of protein structure and structure-based activation
