Computational design of co-assembling multi-component protein nanomaterials

Abstract

Molecular self- and co-assembly of proteins into highly ordered symmetric complexes is an elegant and powerful means of patterning matter at the atomic scale and a hallmark of biological systems. Inspired by the exquisite forms and functions achieved by such protein-based molecular machines and materials in nature, my dissertation has focused on the development of methods for the atomically-accurate design of novel symmetric protein complexes. Specifically, I have focused on the design of materials formed through the co-assembly of multiple copies of two or more distinct protein subunits. The ability to design such multi-component materials with high accuracy has remained an outstanding challenge in the field of protein engineering, but offers great potential for a wide range of applications, including vaccine design, targeted delivery, and renewable energy. Here I present the results of my efforts, including the accurate design of five novel tetrahedral and ten novel icosahedral protein complexes formed through the co-assembly of two distinct types of protein subunits. These results represent a significant advance in protein design and nanotechnology, opening the door to a new generation of genetically programmable materials tailored to specific applications.