Stability Of Norwalk Virus Capsid Protein Interfaces Evaluated By In Silico Nanoindentation

Studying the mechanical properties of viral capsids can give several insights into not only the lifecycle of the virus, but also into potential drug targets to thwart the progression of viral infection. Nanoindentation using an atomic force microscope is a useful technique for determining structural properties of small molecules and particles, and is commonly used to study viral capsids. This technique utilizes the probe of the microscope to push down on the capsid and record the forces along the indentation path. We ran this experiment in silico where we simulated the nanoindentation of Norwalk virus capsids using molecular dynamics. Running a simulation of the nanoindentation allowed us to observe the capsid deformation in much more detail than is possible experimentally. We were able to identify a distinctly weak interface in the Norovirus capsid. This interface might be the initial interface to disassemble during viral uncoating in the host cell for infection to proceed. Strengthening this interface might prevent uncoating and further infection. We identified three sites in this weak interface that may prove to be good drug targets for an antiviral treatment of Norwalk virus. Our study culminated in a publication in the journal Frontiers in Bioengineering and Biotechnology (Boyd, K. J., Bansal, P., Feng, J., & May, E. R. (2015). Stability of Norwalk Virus Capsid Protein Interfaces Evaluated by in Silico Nanoindentation. Frontiers in Bioengineering and Biotechnology, 3(July), 1–8. doi:10.3389/fbioe.2015.00103)