The Hepatitis B Capsid through the Computational Microscope - Jodi Hadden

Hepatitis B virus is a major cause of liver disease. Researchers are endeavoring to develop new treatments against the virus that target its capsid, a protein shell that encases the viral genome and drives its delivery to the host cell-nucleus. Numerous drugs that disrupt the capsid have been identiifed, but their mechanisms of action are incompletely understood. The PI has been utilizing Blue Waters as a computational microscope since 2015 to investigate the intact hepatitis B capsid and the effect of drugs on its structure, dynamics, and assembly. Here, the PI will describe her continued efforts to characterize the capsid as a drug target, including important new discoveries regarding drug binding modes, cooperativity in drug-uptake, and mechanisms of drug resistance. Importantly, the results produced by this study were inaccessible to experimental methods and were made possible only through molecular dynamics simulations of multimillion-atom capsid systems enabled by Blue Waters.