Jodi A Hadden, Juan R Perilla, Christopher John Schlicksup, Balasubramanian
Venkatakrishnan, Adam Zlotnick, and Klaus Schulten.
All-atom molecular dynamics of the HBV capsid reveals insights into
biological function and cryo-EM resolution limits.
eLife, 7:e32478, 2018.
(PMC: PMC5927769)
HADD2018
The hepatitis B virus capsid represents a promising therapeutic target.
Experiments suggest the capsid must be flexible to function; however,
capsid structure and dynamics have not been thoroughly characterized in
the absence of icosahedral symmetry constraints. Here, all-atom molecular
dynamics simulations are leveraged to investigate the capsid without
symmetry bias, enabling study of capsid flexibility and its implications for
biological function and cryo-EM resolution limits. Simulation results confirm
flexibility and reveal a propensity for asymmetric distortion. The capsid’s
influence on ionic species suggests a mechanism for modulating the display
of cellular signals and implicates the capsid’s triangular pores as the location
of signal exposure. A theoretical image reconstruction performed using
simulated conformations indicates how capsid flexibility may limit the
resolution of cryo-EM. Overall, the present work provides functional insight
beyond what is accessible to experimental methods and raises important
considerations regarding asymmetry in structural studies of icosahedral
virus capsids.
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