TCB Publications - Abstract

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 capsidís influence on ionic species suggests a mechanism for modulating the display of cellular signals and implicates the capsidís 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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