Furthering characterization of the hepatitis B virus capsid as a drug target: Simulations to investigate quasi-equivalence and cooperativity in drug binding

Jodi Hadden, University of Delaware

Usage Details

Hepatitis B virus (HBV) causes severe liver disease; 250 million people are infected, and there is no cure. The capsid of HBV, a protein shell that encases the viral genome and orchestrates its delivery to the host cell nucleus, is of great interest as a drug target. Drug molecules are known to bind quasi-equivalent locations on the capsid termed B and C sites. Previous simulations show that B and C sites exhibit key structural differences. We are now performing simulations of the capsid complexed with the drug HAP18 in (i) both B and C sites, (ii) only B sites, and (iii) only C sites. Based on simulation data obtained to date, we have learned that these three patterns of drug occupancy produce unique effects on capsid morphology. Preliminary analysis also suggests the structural mechanism for cooperative drug binding. Our observations were inaccessible to experiments, yet enabled by the “computational microscope.”