Unveiling the functions of the HIV-1 and hepatitis B virus capsids through the computational microscope
Viruses represent a serious public health threat and millions of people are affected annually by viral diseases. In an effort to prevent and combat viral infection, researchers worldwide are endeavoring to develop vaccines and drug-based treatments, particularly targeting virus capsids. Capsids are proteinacious containers than encase the viral genome. All-atom description of virus capsids has proven to be extremely valuable in accurately characterizing protein-protein interfaces and in revealing novel interactions between capsids and restriction factors/drug molecules. Here, innovations in computational modeling and simulation techniques will enable (1) determination of the atomistic structure of the full-length hepatitis B virus capsid capable of packaging pregenomic RNA, and (2) elucidation of the functional role of the HIV-1 capsid during reverse transcription. To overcome size-scale and time-scale limitations, canonical molecular dynamics simulations will be performed in tandem with enhanced sampling techniques. Remarkably, the amount of sampling required for the two ambitious aims proposed in the present study can only be achieved on a petascale machine such as Blue Waters.