During the replication of many viruses, hundreds to thousands of protein subunits assemble around the viral nucleic acid to form a protein shell called a capsid. Within their host organism, most viruses form one particular structure with astonishing fidelity;yet, recent experiments demonstrate that capsids can assemble with different sizes and morphologies to accommodate nucleic acids, inorganic nanoparticles, and polyanions with different sizes. This project will use computational models to determine the features of viral proteins and their cargoes that enable assembly to be so precise and yet so adaptable. We develop simplified representations of viral proteins and cargoes that range from rigid spheres to fluctuating polymers to model nucleic acids. With these models we will develop experimentally testable predictions for the mechanisms by which viral proteins dynamically encapsidate these objects, and which factors direct the assembly process towards a particular size and morphology. These coarse-grained models of the overall assembly process will be validated and guided by atomic-resolution simulations that examine the dynamic conformations of viral proteins.
Viral diseases and acquired drug resistance by viruses are major biomedical challenges. The most effective antiviral treatments fight acquired resistance by using use multiple drugs to target several steps in the infection process, but relatively few treatments target viral assembly. By identifying the features that make viral assembly successful, we can learn to block it and thereby create novel antivirus therapies.
|Hagan, Michael F (2014) Modeling Viral Capsid Assembly. Adv Chem Phys 155:1-68|
|Perlmutter, Jason D; Qiao, Cong; Hagan, Michael F (2013) Viral genome structures are optimal for capsid assembly. Elife 2:e00632|
|Ruiz-Herrero, Teresa; Velasco, Enrique; Hagan, Michael F (2012) Mechanisms of budding of nanoscale particles through lipid bilayers. J Phys Chem B 116:9595-603|
|Yu, Naiyin; Hagan, Michael F (2012) Simulations of HIV capsid protein dimerization reveal the effect of chemistry and topography on the mechanism of hydrophobic protein association. Biophys J 103:1363-9|
|Patel, Amish J; Varilly, Patrick; Jamadagni, Sumanth N et al. (2012) Sitting at the edge: how biomolecules use hydrophobicity to tune their interactions and function. J Phys Chem B 116:2498-503|
|Ni, Peng; Wang, Zhao; Ma, Xiang et al. (2012) An examination of the electrostatic interactions between the N-terminal tail of the Brome Mosaic Virus coat protein and encapsidated RNAs. J Mol Biol 419:284-300|
|Yang, Yasheng; Barry, Edward; Dogic, Zvonimir et al. (2012) Self-assembly of 2D membranes from mixtures of hard rods and depleting polymers(). Soft Matter 8:707-714|
|Dhason, Mary S; Wang, Joseph C-Y; Hagan, Michael F et al. (2012) Differential assembly of Hepatitis B Virus core protein on single- and double-stranded nucleic acid suggest the dsDNA-filled core is spring-loaded. Virology 430:20-9|
|Hagan, Michael F; Elrad, Oren M; Jack, Robert L (2011) Mechanisms of kinetic trapping in self-assembly and phase transformation. J Chem Phys 135:104115|
|Giomi, L; Mahadevan, L; Chakraborty, B et al. (2011) Excitable patterns in active nematics. Phys Rev Lett 106:218101|
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