CAREER: Physics of Virus Structure: Energetics and Dynamics

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TECHNICAL SUMMARY:This is a CAREER award supports theoretical research and education at the interface of condensed matter physics and biology. The aim of the proposed research is to set up a statistical mechanical investigation of viral structure focusing on the right (coarse-grained) level of description to capture the essential physics, yet include sufficient biochemical details to develop verifiable models to elucidate viral assembly. In particular, the following major questions will be investigated: (i) What are the relevant thermodynamic control parameters that determine the size and shape of empty capsids? (ii) What is the effect of the enclosed genome on the size and shape of capsid, in particular for the case of co-assembly (where genome triggers the formation process)? And (iii) what are the effects of all these factors on the kinetics of self-assembly? Important issues in the assembly of empty capsids are the relation between protein shape, hydrophobic and screened-coulomb interactions between them, and the geometry of the icosahedral, cylindrical and conical assemblies. The research will focus on the statistical mechanics of viral self-assembly, both equilibrium and nonequilibrium. Since capsid assembly is akin to a thermodynamic phase transition, nucleation theory will be used for the kinetics. Furthermore, to elucidate the simplest physical role played by an encapsidated chain in determining the preferred size of a virus, the self-consistent field theory of polyelectrolyte adsorption will be extended to confined geometries. Of interest is how the free energy of viral particles is influenced by genome length and the strength of genome/capsid attractive interaction. In view of the complexity of the physics, the analytical theory is to be augmented by scaling methods, numerical investigations, and computer simulation. In particular, the PI will perform a series of Monte Carlo and Brownian dynamics computer simulations to explore the equilibrium and kinetic aspects of viral self-assembly. Our simulations involve a system of model capsid proteins for investigating the selection of shell size and symmetry among capsids.This award also contributes to the education of undergraduate, graduate and postgraduate students, and particularly to the training of the next generation of condensed matter and biological physicists. An outreach program for K-12 level teachers in the Riverside and San Bernardino counties, and workshops for women aim to improve participation of underrepresented groups in science. NON-TECHNICAL SUMMARY:This is a CAREER award supports theoretical research and education at the interface of condensed matter physics and biology. A fundamental step in the replication of a viral particle is the self-assembly of its rigid shell (capsid) from its constituent proteins and enclosed genome. The physics of viruses is exceptionally rich. It involves understanding the behavior of large molecules (polymers) in confined volumes and the co-operative growth of genomes and capsids. While the in vitro and in vivo assemblies of viruses are considered as the paradigm for self-assembly in biology, the physical principles that underlie virus structure are only beginning to be understood. The PI will carry out theoretical research using the tools of statistical physics to attack important problems aimed at improving our understanding of virus structure and assembly.Since capsids play a vital role in genome replication and intercellular movement of viruses, understanding viral assembly may be critical in the development of new anti-viral therapies and systematic treatment of viral infection. This research also connects with emerging areas of materials science - the synthesis of viral nano-containers for enclosing non-genetic material and designing novel biomimetic materials. Further, as viruses infect all kinds of hosts (bacteria, plants, and animals) with various degrees of severity (from the common cold to AIDS), there is keen interest among students at all levels to understand the mechanisms governing viral life cycle.This award also contributes to the education of undergraduate, graduate and postgraduate students, and particularly to the training of the next generation of condensed matter and biological physicists. An outreach program for K-12 level teachers in the Riverside and San Bernardino counties, and workshops for women aim to improve participation of underrepresented groups in science.