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Retroviruses are parasites that pose a major health threat to humans (for example in case of HIV) and other animals (for example in case of RSV, M-PMV, MLV, and many more viruses). After a retrovirus hijacks a cell, the infected cell produces multiple copies of the virus which are then released into the host's bloodstream. These newly released viruses must mature before they can infect other cells. A strategy for preventing virus spread is therefore, to lock the viral particles in their immature, non-infectious state. However, to render the immature virus an attractive target for structure-based drug development one needs to know its chemical structure. Unfortunately, the complexity and size of the viral particle ― an incomplete hexagonal shell with a size close to 100 nm ― have prevented the experimental determination of the chemical, namely atomic level, structure of the virus. As reported recently, a team of computational and experimental researchers have provided an atomic structure of the immature retroviral lattice for the Rous Sarcoma Virus. The multi-domain RSV model was derived through a combination of state-of-the-art modeling techniques, including, cryo-EM-guided homology modeling, large-scale molecular dynamics simulations using enhanced sampling capabilities available in NAMD, together with experimental measurements such as X-ray crystallography and a wealth of biochemical data. Particularly, the model reveals novel features of the packing and dynamics of the immature capsid protein with implications for the maturation process and confirms the stabilizing roles of the so-called upstream and downstream domains of the immature RSV. More information is available on our retrovirus website, and in a highlight video.
- Mapping mechanical force propagation through biomolecular complexes. Nano Lett., 2015. In Press.
- Dynamic profiling of double-stranded RNA binding proteins. Nucleic Acids Res., 2015. In Press.
- Macromolecular crystallography for synthetic abiological molecules: Combining xMDFF and PHENIX for structure determination of cyanostar macrocycles. Journal of the American Chemical Society, 137:8810-8818, 2015.