Edward Egelman received a collaborative research grant with Emory University.
Molecular self-assembly is a fundamental principle of life, with cells having mastered this process to encode incredible diversity of function. Helical protein assemblies, including collagen, keratin, F-actin, and tubulin, among others, organize much of the intracellular and extracellular structure, and direct all movement, e.g., flagellate locomotion, cytoplasmic streaming, muscle contraction, etc. The ability to emulate such functions by designing synthetic protein assemblies would transform modern molecular science, with far-reaching applications including locomotion, controlled release, directional transport, dynamic switching, and shape-selective catalysis. However, structurally ordered supramolecular materials on the nanometer length-scale are the most challenging to rationally construct and the most difficult to structurally analyze. The size of these extended protein assemblies and the complexity of inter-subunit interactions present a significant challenge to current computational design methods. In this proposal, we will establish, validate, and make available to the community a novel framework for the targeted design of synthetic protein assemblies at atomic-level accuracy. Enabled by the combined expertise of the three investigators involved, this approach will merge significant advances in modeling and computational design with never-before-possible experimental techniques for structural determination at the atomic level. On the way to developing our framework, we will answer fundamental questions of acute significance to biology and biophysics: from understanding of the functional roles of helical protein assemblies in biology to shedding light on the robustness of protein quaternary structure in sequence space.
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