All-atom molecular dynamics of the HBV capsid reveals insights into biological function and cryo-EM resolution limits.
| Autor: | Hadden JA; Department of Chemistry and Biochemistry, University of Delaware, Newark, United States., Perilla JR; Department of Chemistry and Biochemistry, University of Delaware, Newark, United States., Schlicksup CJ; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States., Venkatakrishnan B; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States., Zlotnick A; Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, United States., Schulten K; Department of Physics, University of Illinois at Urbana-Champaign, Urbana, United States.; Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, United States. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | ELife [Elife] 2018 Apr 27; Vol. 7. Date of Electronic Publication: 2018 Apr 27. |
| DOI: | 10.7554/eLife.32478 |
| Abstrakt: | 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. Competing Interests: JH, JP, CS, BV, KS No competing interests declared, AZ A.Z. has an interest in a biotechnology company and acknowledges a conflict of interest. (© 2018, Hadden et al.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|