Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Computational Design Strategies for RNA Nanostructures

Recent developments in the field of nanobiology have significantly expanded the possibilities for new materials in the treatment of many diseases including cancer. The field of nanobiology, which is essentially defined as the control and design of biological materials that have dimensions commonly less than 100 nm holds great promise in the therapeutic arena due to the ability to design nanoparticles with specific properties. RNA represents a relatively new molecular material for the development of these biologically oriented nano devices. We have created various computational strategies that permit a user to design RNA based nanoparticles (1-6). These strategies ultimately provide a means to determine a set of nucleotide sequences that can assemble into a desired RNA nano complex. Examples include our RNAJunction database which forms one of the foundations for our RNA nanodesign. The database contains structural and sequence information for RNA helical junctions and kissing loop interactions. These junctions were extracted automatically from the PDB database by a special scanning algorithm. The database also contains the results from applying molecular mechanics and structural clustering techniques to the motifs. These motifs can be searched for in a variety of ways, providing a source for RNA nano building blocks. Another computational tool, NanoTiler, permits a user to interactively and automatically construct RNA-based nanoscale shapes. NanoTiler provides a 3D graphical view of the objects to be designed. NanoTiler provides the means to work interactively, or with a scripting language, on the design process even though the precise RNA sequences may not yet be specified. NanoTiler can use the 3D motifs found in the RNAJunction database with those derived from specified RNA secondary structure patterns to build the defined RNA nano shape. Then, with the aid of special sequence design algorithms a set of sequences can be predicted that can potentially self-assemble into a structure with the desired shape and functionality. Finally, another computational tool, RNA2D3D, permits the modeling of RNA 3D structures based upon RNA secondary structure input. RNA nanoshapes can be modeled using this paradigm. Examples will be shown that illustrate the use of these various design strategies and issues related to characterizing the ability of these RNA nanostructures to self-assemble.

References and Footnotes
  1. Bindewald E, Grunewald C, Boyle B, O'Connor M, Shapiro BA. Computational strategies for the automated design of RNA nanoscale structures from building blocks using NanoTiler. J. Mol. Graph. Model. 27(3): 299-308, (2008).
  2. Shapiro B, Bindewald E, Kasprzak W, Yingling Y. (Gazit E, Nussinov R, eds.) Protocols for the In Silico Design of RNA Danostructures. In: Nanostructure Design Methods and Protocols. Totowa, NJ: Humana Press; (2008). p. 93-115
  3. Martinez HM, Maizel JV, Shapiro BA. RNA2D3D: A program for generating, viewing, and comparing 3-dimensional models of RNA. J. Biomol. Struct. Dyn. 25: 669-83, (2008).
  4. Severcan I, Geary C, Jaeger L, Bindewald E, Kasprzak W, Shapiro B. (Alterovitz G, Benson R, Ramoni M eds.) Computational and Experimental RNA Nanoparticle Design. In: Automation in Genomics and Proteomics: An Engineering Case-Based Approach. Hoboken: Wiley Publishing; (2009). p. 193-220.
  5. Bindewald E, Hayes R, Yingling YG, Kasprzak W, Shapiro BA. RNAJunction: a database of RNA junctions and kissing loops for three-dimensional structural analysis and nanodesign. Nucleic Acids Res. 36: D392-7, (2008).
  6. Yingling YG, Shapiro BA. Computational design of an RNA hexagonal nanoring and an RNA nanotube. Nano Lett. 7(8): 2328-2334, (2007).

Bruce A. Shapiro

Center for Cancer Research
Nanobiology Program
National Cancer Institute
Frederick, MD 21702

Tel: 301-846-5536
Fax: 301-846-5598