De Novo Scaffold Design: From Membrane β-Barrels to ɑ-helical Repeat Oligomers

Abstract

De novo design of new protein folds, shapes, and features opens up new avenues for functional design. My thesis work covers the de novo design of membrane beta barrels, important considerations for making new metal binding proteins, and the design of large sets of homo-oligomers with a wide variety of pocket shapes and sizes. This work aims to shed structural and functional insights necessary to create well behaved proteins with specific desired features without being limited to the natural proteins that have been characterized. The quick and accurate generation of new protein scaffolds with a variety of folds or pocket sizes will contribute to enabling further functional design of de novo membrane pores, protein catalysts, and small-molecule binders.