Computational studies of virus assembly around nucleic acids and on lipid membranes
November 11, 2014 - 10:00am
Klaus 1116 East
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, structure, and sequence of the nucleic acid could promote biomedical efforts to block viral propagation and guide the reengi-neering of capsids for gene therapy applications.
This talk will describe coarse-grained models of capsid proteins and NAs which enable dynamical simulations of the assembly process. With these models, we investigate how assembly efficiency and mechanisms depend on biophysical parameters, such as RNA length and structure, solution conditions, and capsid protein charge. 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. We then show that assembly can proceed through two qualitatively different classes of pathways, which can be tuned by controlling solution conditions or changing the capsid protein charge. Time permitting, we will also dis-cuss how viruses assemble on a substrate with a different topology – an enveloping lipid membrane.