Comparative analysis of the extent of protein-protein interactions in icosahedral viral capsids.

Nonenveloped viruses package, carry, and deliver their genomes to the targeted cells using protein shells known as capsids. The viral capsids come in different shapes and sizes, most exhibiting helical or icosahedral symmetries. Here, we analyzed 634 icosahedral capsids at high resolution (<4 Å) from 39 virus families with T-numbers ranging from 1 to 9 and evaluated the aggregated buried surface areas (BSAs) at the unique interfaces as a measure of capsid strength and protein-protein interactions (PPIs). The BSAs were further analyzed relative to their capsid diameters and the calculated molecular weight (MW) of coat protein subunits (CPs) occupying the icosahedral asymmetric unit (IAU). Our results show that naturally occurring viral capsids exhibit stronger PPIs relative to non-native and/or engineered capsids. Interestingly, the "T = 2" capsids cluster distinctly, exhibiting weaker PPIs relative to their capsid size and subunit MWs. Furthermore, the normalized BSAs by the MW of the CPs present in the IAU are fairly constant across different capsids, suggesting that the extent of the PPIs is proportional to the CP size with a few exceptions (e.g., "T = 2" capsids). We also identified the range of capsid diameters and MWs of CPs forming different T = number capsids, which suggest a CP of 30-50 kDa can be used to build any quasi-equivalent capsid with T-numbers 1-9. Furthermore, we identified the strongest capsids available at various diameters at 25 Å intervals. Taken together, in addition to the targeting specificities, the results from this study are useful for choosing viral capsids for biomedical applications.