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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Capsid / chemistry*
  • Capsid / ultrastructure*
  • Cryoelectron Microscopy*
  • Hepatitis B virus / chemistry*
  • Hepatitis B virus / ultrastructure*
  • Molecular Dynamics Simulation*
  • Protein Conformation