Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Thursday Speaker Abstracts

THE STRUCTURE AND PHYSICAL PROPERTIES OF A BACTERIOPHAGE GENOME RESOLVED THROUGH ATOMISTIC MOLECULAR DYNAMICS SIMULATION Kush Coshic ; Christopher M Maffeo 2 ; David Winogradoff 2 ; Aleksei Aksimentiev 1,2 ; 1 University of Illinois, Urbana-Champaign, Center for Biophysics and Quantitative Biology, Urbana, IL, USA 2 University of Illinois, Urbana-Champaign, Physics, Urbana, IL, USA While atomic structures of protein capsids have been resolved for several viruses, the structural organization of their genomes still remains largely unknown. One such viral species is HK97 bacteriophage, for which experiments have characterized the packaging mechanism and resolved its protein capsid with atomistic resolution. Here, we report a computational reconstruction of a complete bacteriophage HK97 viral particle at atomistic resolution, including its genome, obtained from a series of simulations gradually increasing in resolution. In a typical simulation, a 37 kb DNA was forced into a viral capsid by local force, mimicking the action of the packaging motor, with or without an additional torque that twisted the molecule as it was packaged. The assembled particle was simulated at several resolutions, including a 26 million atom explicit- solvent model of a complete virion that contained both the protein capsid and the DNA. Measurements of the internal pressure throughout the simulations were consistent with experimental data whereas the SAXS profile derived from the resulting structures matched the corresponding experiment. The results of all-atom simulations revealed the pattern of DNA- protein capsid interactions and striking DNA mobility within the packaged virion. The complete atomistic structure of a packaged virion uncovers the detailed genome-capsid interactions, offering exciting new avenues for the development of antiviral drugs.

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