Design of Protein Biomaterials Through Tailored Shape and Packing Strategies of Patchy Particles

Major Goals: The ability to control the assembly of materials is paramount to the design and production of smart materials with novel properties. However, programmed assembly has proven difficult: nucleic acids can be programmed to assemble, but in general do not form structures extensive enough to be useful for many applications. Conversely, polymers that can form extensive structures, such as plastics, have interactions that are relatively non-directed and are not sufficiently information rich to program. Our research aims to ascertain whether proteins that can be produced in bulk can be generally programmed to self-assemble into higher order structures based on relatively non-directed electrostatic interactions, effectively encompassing the information rich nature of nucleic acids and the relatively non-directed and extensive assembly capabilities of plastics and other materials. Under a previous grant from ARO, we developed a computational model of a supercharged green fluorescent protein (a protein with added charges on specific sites) capable of reproducing and predicting experimental findings by our collaborator at UT Austin. Our computational model was based on treating interacting proteins as patchy particles. Prior to that grant, the state-of-the-art in simulating proteins as patchy particles was based on models developed by others in which proteins are treated as spheres. Because we know how important shape is to the assembly of nanoparticles and colloids, we aimed to develop the first patchy protein model where protein shape is explicitly included. We successfully parameterized our patchy shape model to account for anisotropic molecular shape and attractive interactions corresponding to the crystallographic interfaces of these proteins. The model was successful in rationalizing the experimentally observed formation of protomers (small assemblies of proteins) and a joint paper was published in Nature Chemistry and was featured as the front cover.