(151h) A Molecular Model for the Thermodynamic Stability of Hepatitis B Virus

We establish an efficient and appropriate thermodynamic model for the stability of a virus nucleocapsid particle. For the Hepatitis B virus (HBV), an effective coarse-grained model is constructed, which includes all pertinent molecular components (i.e., capsid proteins and their flexible domains, nucleic acids, and ions in the electrolyte background) and solvent-mediated interactions: the hydrophobic association of capsid subunits, the electrostatic interactions, the entropy, the excluded volume, and the macromolecular crowding effects. Based on such an explicit framework, we investigate the stability of the viral particle with a focus on physiological cellular conditions. We consider the free energy of the empty capsid formation and the interaction free energy of pre-genomic RNA and C-terminal domain (CTD) of the capsid proteins. In comparison with experimental investigations for HBV, our model presents appropriate equilibrium values for the capsid assembly and supports the balanced electrostatic interaction hypothesis for the capsid stability and genome encapsidation. Moreover, this model presents a generic theoretical approach for determining the optimal genome length of viral particles.