The presented work is the application of recent methodologies on modeling and
simulation of single stranded RNA viruses. We first present the methods of modeling
RNA molecules using the coarse-grained modeling package, YUP. Coarse-grained
models simplify complex structures such as viruses and let us study general behavior of
the complex biological systems that otherwise cannot be studied with all-atom details.
Second, we modeled the first all-atom T=3, icosahedral, single stranded RNA
virus, Pariacoto virus (PaV). The x-ray structure of PaV shows only 35% of the total
RNA genome and 88% of the capsid. We modeled both missing portions of RNA and
protein. The final model of the PaV demonstrated that the positively charged protein N-
terminus was located deep inside the RNA. We propose that the positively charged N-
terminal tails make contact with the RNA genome and neutralize the negative charges in
RNA and subsequently collapse the RNA/protein complex into an icosahedral virus.
Third, we simulated T=1 empty capsids using a coarse-grained model of three
capsid proteins as a wedge-shaped triangular capsid unit. We varied the edge angle and
the potentials of the capsid units to perform empty capsid assembly simulations. The final
model and the potential are further improved for the whole virus assembly simulations.
Finally, we performed stability and assembly simulations of the whole virus using
coarse-grained models. We tested various strengths of RNA-protein tail and capsid
protein-capsid protein attractions in our stability simulations and narrowed our search for
optimal potentials for assembly. The assembly simulations were carried out with two
different protocols: co-transcriptional and post-transcriptional. The co-transcriptional
assembly protocol mimics the assembly occurring during the replication of the new RNA.
Proteins bind the partly transcribed RNA in this protocol. The post-transcriptional
assembly protocol assumes that the RNA is completely transcribed in the absence of
proteins. Proteins later bind to the fully transcribed RNA. We found that both protocols
can assemble viruses, when the RNA structure is compact enough to yield a successful
virus particle. The post-transcriptional protocol depends more on the compactness of the
RNA structure compared to the co-transcriptional assembly protocol. Viruses can exploit
both assembly protocols based on the location of RNA replication and the compactness
of the final structure of the RNA.PhDCommittee Chair: Stephen C. Harvey; Committee Member: Adegboyega Oyelere; Committee Member: Loren Williams; Committee Member: Rigoberto Hernandez; Committee Member: Roger Wartel
