Journal
RNA
Volume 16, Issue 11, Pages 2252-2262Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.2102210
Keywords
in vitro selection; random pool; aptamer pool design; RNA/DNA secondary structure; genetic algorithm; ATP aptamer
Categories
Funding
- Natural Sciences and Engineering Council of Canada (NSERC)
- Canadian Foundation for Innovation (CFI)
- Ontario Research Fund (ORF)
- Carleton University
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It is well known that using random RNA/DNA sequences for SELEX experiments will generally yield low-complexity structures. Early experimental results suggest that having a structurally diverse library, which, for instance, includes high-order junctions, may prove useful in finding new functional motifs. Here, we develop two computational methods to generate sequences that exhibit higher structural complexity and can be used to increase the overall structural diversity of initial pools for in vitro selection experiments. Random Filtering selectively increases the number of five-way junctions in RNA/DNA pools, and Genetic Filtering designs RNA/DNA pools to a specified structure distribution, whether uniform or otherwise. We show that using our computationally designed DNA pool greatly improves access to highly complex sequence structures for SELEX experiments (without losing our ability to select for common one-way and two-way junction sequences).
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