Statistical mechanical prediction of ligand perturbation to RNA secondary structure and application to riboswitches
| Autor: | Fareed Aboul-ela, Osama Alaidi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Riboswitch
Models Statistical 010304 chemical physics Chemistry RNA Conformation RNA General Chemistry Ligands 010402 general chemistry Ligand (biochemistry) Non-coding RNA 01 natural sciences Protein tertiary structure 0104 chemical sciences Nucleic acid secondary structure Computational Mathematics 0103 physical sciences Biophysics Nucleic Acid Conformation Thermodynamics Protein secondary structure |
| Zdroj: | Journal of Computational Chemistry. 41:1521-1537 |
| ISSN: | 1096-987X 0192-8651 |
| DOI: | 10.1002/jcc.26195 |
| Popis: | The realization that noncoding RNA is implicated in numerous cellular processes, makes it imperative to understand and predict RNA-folding. RNA secondary structure prediction is more tractable than tertiary structure or protein structure. Yet insights into RNA structure-function relationships are complicated by coupling between RNA-folding and ligand-binding. Here, perturbations to equilibrium secondary structure conformational distributions for two riboswitches are calculated in the presence of bound cognate ligands. This work incorporates a key factor coupling ligand binding to RNA conformation but not considered in most previous calculations: the differential affinity of the ligand for a range of RNA-folding intermediates. Significant shifts in the free energy landscape (FEL) due to the ligand occur for transcripts of lengths corresponding to the "decision window," following transcription of the so-called anti-terminator helix. The results suggest how ligand perturbation can stabilize the formation of an intermediate conformation, readily facilitating terminator hairpin formation in the full-length riboswitch. |
| Databáze: | OpenAIRE |
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