Fig. 2.

An overview of the modeling methodology including flexibility data from MD simulations and optional helical linkers subject to controlled distortions. RNA building blocks obtained from a structural database, such as RNAJunction or PDB, are used to build a rigid model of a nanoparticle. In case the full structure model does not close, the junctions used and/or subassemblies of the full nanostructure can be subjected to Molecular dynamics (MD) simulations in order to characterize their flexibility. One can also explore the structural parameters required to affect closure with the help of a program such as RNA2D3D, using the results as parameters in searches for MD states of the building blocks that could assemble into a fully closed structure (bottom left and Fig. 7A). Combinatorial searches can be utilized to explore the entire set of MD trajectories of the building blocks (with or without any parameter constraints) in order to find structure closing combinations (bottom center and Fig. 8). The most flexible approach combines the MD states of junctions or subassemblies with the linker helices which can be distorted independently of the MD states, but within the MD-indicated range of distortions, in order to affect full nanostructure closure (bottom right and Fig. 9). The last two closure search schemes were accomplished with PyMOL and NanoTiler scripts.