Physics of Viral Structure and Assembly

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Technical SummaryThis award supports theoretical research and education on the structural transformations that occur in viral capsid shells. Viral shells have found applications in materials research where they are used as nanocontainers with a stable surface structure that can be genetically altered. Recent biophysical studies of viral shells have shown that viral shells can also be viewed as molecular machines that adopt a range of different structures as part of their natural maturation process. The changes between different shell structures are effected either by successive, cooperative conformational changes of hundreds of capsid proteins or by a sequence of carefully controlled chemical reactions in response to changes in solution conditions or internal pressure. The main objective of this project is to develop simple analytical and numerical methods firmly based on theoretical physics that can be used to describe these cooperative structural changes and chemical reactions and to apply them in particular to the case of the bacteriophage virus Hong-Kong 97, or HK97. During maturation the protein shell of HK97 evolves from a fragile protein assembly to a chainmail of covalently linked protein domains. Experimentalists working on HK97 have proposed a range of ideas, such as hexon symmetry breaking as an error correction mechanism during assembly, thermal Brownian ratchets as a mechanism for translating chemical reactions into large-scale structural changes and for generating work, and cooperative mobility of groups of proteins as a mechanism for effecting structural change. The PIs aim to develop and evaluate these ideas from a physical perspective. They will apply methods that have been developed to describe collective conformational changes, specifically the Ginzburg-Landau theory of phase transitions. The PIs will develop a single Ginzburg-Landau description for the sequence of HK97conformational transitions that could be extended to other viral shells and provide conceptual unity of viral maturation. These methods could provide new theoretical tools and training to young physical scientists interested in working on problems in biological physics. Materials scientists working on virus-based materials applications would be provided with theoretical methods and numerical models for studies of viral shells assembled from active capsid proteins, such as HK97 subunits, that can carry out a controlled program of conformational and chemical change.Non-Technical SummaryThis award supports theoretical research that aims to understand the structure of the protein shells that surround viruses. Scientists have found numerous practical uses for virus protein shells outside the Life Sciences. They are used as support structures for the molecular scale assembly of materials that can be "designed" by directed assembly. Tiny metallic wires, solar cells, batteries, and fuel cells that have dimensions on the scale of large molecules have all been assembled from viral shells. In these applications, the shell proteins play a passive "support" role. A new generation of applications of viral shells will be based on the exquisitely coordinated collective physical and chemical transformations that take place in viral shells, progressively strengthening it. The PIs aim to develop a general description of this maturation process based on the analysis of the best studied case: the Hong-Kong97 virus. This description may act as a guide in the design of new applications of viral shells.