Professor Michael Hagan, Brandeis University. Virus assembly around RNA and on a membrane. R.B. Woodward Lectures in the Chemical Sciences, Physical Chemistry Seminar.
Abstract: For many viruses, the spontaneous assembly of a capsid shell around the nucleic acid (NA) genome is an essential step in the viral life cycle. Understanding how this process depends on the charge and structure of the nucleic acid could promote biomedical efforts to block viral propagation and guide the reengineering of capsids for gene therapy applications.
This talk will describe coarse-grained models of capsid proteins and NAs with which we investigate the dynamics and thermodynamics of virus assembly. In contrast to recent theoretical models, we find that capsids spontaneously ‘overcharge’; that is, the NA length which is kinetically and thermodynamically optimal possesses a negative charge greater than the positive charge of the capsid. When applied to specific virus capsids, the calculated optimal NA lengths closely correspond to the natural viral genome lengths. These results suggest that the features included in this model (i.e. electrostatics, excluded volume, and NA tertiary structure) play key roles in determining assembly thermodynamics and consequently exert selective pressure on viral evolution. Finally, I will discuss how viruses assemble on a substrate with a different topology - an enveloping lipid membrane.