Abstract
During the lifecycle of many single-stranded RNA viruses, including many
human pathogens, a protein shell called the capsid spontaneously assembles
around the viral genome. Understanding the mechanisms by which capsid proteins
selectively assemble around the viral RNA amidst diverse host RNAs is a key
question in virology. In one proposed mechanism, sequence elements (packaging
sites) within the genomic RNA promote rapid and efficient assembly through
specific interactions with the capsid proteins. In this work we develop a
coarse-grained particle-based computational model for capsid proteins and RNA
which represents protein-RNA interactions arising both from non-specific
electrostatics and specific packaging sites interactions. Using Brownian
dynamics simulations, we explore how the efficiency and specificity of assembly
depend on solution conditions (which control protein-protein and nonspecific
protein-RNA interactions) as well as the strength and number of packaging
sites. We identify distinct regions in parameter space in which packaging sites
lead to highly specific assembly via different mechanisms, and others in which
packaging sites lead to kinetic traps. We relate these computational
predictions to in vitro assays for specificity in which cognate viral RNAs are
compete against non-cognate RNAs for assembly by capsid proteins.