This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Satellite tobacco mosaic virus (STMV) is a small satellite virus known to coinfect several species of plants in the presence of tobacco mosaic virus (TMV). Previous experimental studies on this system have provided a high resolution crystal structure for the viral capsid, a somewhat lower resolution structure that allows placement of the backbone of encapsidated RNA [14, 127], and AFM data on the properties of the intact virion and isolated RNA [15,128]. The presence of this data has allowed some hypotheses to be formed on how the virus assembles, but this mechanism is not completely clear, and there is even less information available on how the capsid might disassemble upon entering a host cell. The application of allatom molecular dynamics to this system (www.ks.uiuc.edu/Research/STMV), while challenging, would both provide specific data on the assembly and disassembly of this virus, and aid in the general development of applying molecular dynamics to viral systems. A first series of the all-atom MD simulations of the complete STMV particle has been performed by the Resource using the program NAMD [44] and reported in a joint publication with our collaborator Alex McPherson [13]. In these simulations, which included up to 1,060,000 atoms, the dynamics of the full virion, as well as its components (the capsid and the RNA genome) separately, were observed on a time scale of 10 ns, and analyzed using VMD [49]. Overall, the simulations covered 55 ns of viral dynamics, which required 35 processor-years of computational time at the NCSA Altix supercomputer. The MD study of the complete STMV particle allowed the elucidation of a number of physical properties of the virus, such as the rates of water and ion transport within the particle, distribution of the electric field around the virus, and correlations between the motions of the unit proteins composing the STMV capsid. These characteristics would be difficult or impossible to obtain through experimental means. In the simulations of the complete virion and its isolated components, it was found that the RNA genome of STMV was structurally stable on its own, as was the complete virus, but the capsid without the RNA core was very unstable and collapsed within 5 to 10 ns. These findings agree with recent experimental results from the McPherson lab [15] suggesting that STMV assembly is not mostly capsid protein-driven as assumed previously [14]. Instead, it seems more likely that the protein capsid of STMV arranges itself around a partially preformed RNA core using a concerted assembly mechanism. The Resource has already begun further simulations to study how the STMV particle disassembles when infecting the cell; because of the virion s impressive stability the answer to this question has so far eluded experimentalists. In addition, future studies in collaboration with Jack Johnson (The Scripps Research Institute) and Xiaowei Zhuang (Harvard U.) will attempt to apply these techniques to somewhat larger, human viruses such as poliovirus.
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