Small Molecule-Based Pattern Recognition To Classify RNA Structure
| Autor: | Christopher S. Eubanks, Jordan E Forte, Amanda E. Hargrove, Gary J. Kapral |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Computational biology 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis Nucleic acid secondary structure Small Molecule Libraries 03 medical and health sciences Transactivation Colloid and Surface Chemistry Nucleic acid structure Protein secondary structure HIV Long Terminal Repeat Chemistry RNA Conformation RNA General Chemistry Small molecule Combinatorial chemistry 0104 chemical sciences 030104 developmental biology Principal component analysis Nucleic Acid Conformation RNA Viral |
| Zdroj: | Journal of the American Chemical Society. 139:409-416 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.6b11087 |
| Popis: | Three-dimensional RNA structures are notoriously difficult to determine, and the link between secondary structure and RNA conformation is only beginning to be understood. These challenges have hindered the identification of guiding principles for small molecule:RNA recognition. We herein demonstrate that the strong and differential binding ability of aminoglycosides to RNA structures can be used to classify five canonical RNA secondary structure motifs through principal component analysis (PCA). In these analyses, the aminoglycosides act as receptors, while RNA structures labeled with a benzofuranyluridine fluorophore act as analytes. Complete (100%) predictive ability for this RNA training set was achieved by incorporating two exhaustively guanidinylated aminoglycosides into the receptor library. The PCA was then externally validated using biologically relevant RNA constructs. In bulge-stem-loop constructs of HIV-1 transactivation response element (TAR) RNA, we achieved nucleotide-specific classification of two independent secondary structure motifs. Furthermore, examination of cheminformatic parameters and PCA loading factors revealed trends in aminoglycoside:RNA recognition, including the importance of shape-based discrimination, and suggested the potential for size and sequence discrimination within RNA structural motifs. These studies present a new approach to classifying RNA structure and provide direct evidence that RNA topology, in addition to sequence, is critical for the molecular recognition of RNA. |
| Databáze: | OpenAIRE |
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