TBI server: a web server for predicting ion effects in RNA folding

Abstract

Background: Metal ions play a critical role in the stabilization of RNA structures. Therefore, accurate prediction of the ion effects in RNA folding can have a far-reaching impact on our understanding of RNA structure and function. Multivalent ions, especially Mg²⁺, are essential for RNA tertiary structure formation. These ions can possibly become strongly correlated in the close vicinity of RNA surface. Most of the currently available software packages, which have widespread success in predicting ion effects in biomolecular systems, however, do not explicitly account for the ion correlation effect. Therefore, it is important to develop a software package/web server for the prediction of ion electrostatics in RNA folding by including ion correlation effects.

Results: The TBI web server http://rna.physics.missouri.edu/tbi_index.html provides predictions for the total electrostatic free energy, the different free energy components, and the mean number and the most probable distributions of the bound ions. A novel feature of the TBI server is its ability to account for ion correlation and ion distribution fluctuation effects.

Conclusions: By accounting for the ion correlation and fluctuation effects, the TBI server is a unique online tool for computing ion-mediated electrostatic properties for given RNA structures. The results can provide important data for in-depth analysis for ion effects in RNA folding including the ion-dependence of folding stability, ion uptake in the folding process, and the interplay between the different energetic components.

Fig 1. The user interface of the TBI server.

(a) the job submission page, (b) the notification page, and (c) the result email.

Fig 2. An example for the result text file.

The file includes two parts: the solution condition and the calculated results.

Fig 3. The average binding fraction.

The average binding fraction on each nucleotide of the T2 RNA pseudoknot in 10mM Mg²⁺ and 100 mM Na⁺ at T = 37°C.

Fig 4. The most probable binding mode for the tightly bound ions.

The lowest energy ion binding mode for the T2 RNA pseudoknot at [Mg²⁺] = 10mM, [Na⁺] = 100mM, T = 37°C. The most probable binding sites (nucleotides) are denoted with the orange color in the inset.

Fig 5. An example for the usage of the TBI server.

The server computes the ion binding properties and the electrostatic free energies for T2 RNA (PDB code 2TPK [25]) in a solution with 10 mM Mg²⁺, 100 mM Na⁺, and T = 37°C.

Fig 6. The Mg²⁺-induced folding stability ΔΔG _Mg²⁺ for the T2 pseudoknot.

(a) and (b) show the 3D structures of T2 pseudoknot (the folded state) and the 24-nt A-form helix, respectively; (c) shows the Mg²⁺-induced folding stability.

Fig 7. The binding fraction and the uptake of Mg²⁺ ions as a function of [Mg²⁺].

(a) and (b) show the 3D structures of the T2 pseudoknot (the folded state) and T2 hairpin (the intermediate state), respectively; (c) shows the binding fraction curves for the T2 pseudoknot (black) and the hairpin (red). (d) shows the Mg²⁺ uptake as a function of [Mg²⁺].