Design of Protein Biomaterials Through Tailored Shape and Packing Strategies of Patchy Particles
Abstract
We propose the computational design of a biomaterial from fluorescent proteins. Our comprehensive, shape- driven design approach will be experimentally validated using ordered aggregates of green fluorescent protein (GFP) variants. The project is a joint effort between computational (Glotzer, University of Michigan) and experimental (Ellington, University of Texas, Austin) research groups. Recent experiments demonstrate that virus capsids and smaller proteins can be assembled into binary lattices. However, the predictive design of such materials presents a significant challenge. Existing computational approaches are either atomistic, and therefore limited to just a few protein building blocks, or they employ a highly simplified Ôpatchy sphereÕ approach, where molecular interactions are encoded into a few directional, short-ranged attractive patches on the surface of a colloidal sphere. Here we propose a new Ôpatchy shapeÕ modeling approach, which combines features of more atomistic approaches with the idea of a coarse-grained protein representation. Our approach leverages recent breakthroughs in packing and assembly simulations of colloidal shapes, models of patchy particles and fast, highly efficient parallelized simulation software all developed by Glotzer. Specifically, we aim to represent proteins by their three-dimensional native shape including attractive surface patches. While the model ignores some protein flexibility, it allows for realistic simulations of packing effects, which we believe are equally important as site-specific interactions. Our coarse-grained model will be refined using molecular docking simulations. We aim to design ordered aggregates of GFP and variants, such as cyan or yellow fluorescent protein, with defined morphology and molecular orientation. Our proposed designs will be evaluated experimentally through surface residue modifications that result in supercharged GFP variants. The Ellington lab is capable of producing GFP molecules with excess charges between -30e and +30e. Ordered aggregates realized in the lab will be characterized using a wide range of experimental techniques, including light scattering to test for aggregation, differential scanning fluorimetry to assess thermal stability, and fluorescence resonance energy transfer to validate the structure. The mechanical properties of stable aggregates will be analyzed using rheology. The proposed research is expected to significantly advance methods for the computational design of biomaterials by virtue of a shape-driven approach and by providing a precedent for the experimental realization of such materials with defined structural, mechanical and functional properties. Potential military applications of the proposed design include the development of dense sensor arrays for the detection of chemical and biothreat agents, which can be possibly combined with biological filters to provide protective capability.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 30, 2018
- Source ID
- W911NF1510185
Entities
People
- Sharon Glotzer
Organizations
- Army Contracting Command
- United States Army
- University of Michigan