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Elife. 2018 Apr 27;7. pii: e32478. doi: 10.7554/eLife.32478.

All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits.

Author information

1
Department of Chemistry and Biochemistry, University of Delaware, Newark, United States.
2
Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States.
3
Department of Physics, University of Illinois at Urbana-Champaign, Urbana, United States.
4
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, United States.

Abstract

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.

KEYWORDS:

Cryo-EM resolution; Hepatitis B Virus; Molecular Dynamics Simulation; Single-Particle Image Reconstruction; Virus Capsid; molecular biophysics; none; structural biology

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