The energetics of small internal loops in RNA

Abstract

The energetics of small internal loops are important for prediction of RNA secondary and tertiary structure, selection of drug target sites, and understanding RNA structure–function relationships. Hydrogen bonding, base stacking, electrostatic interactions, backbone distortion, and base‐pair size compatibility all contribute to the energetics of small internal loops. Thus, the sequence dependence of these energetics are idiosyncratic. Current approximations for predicting the free energies of internal loops consider size, asymmetry, closing base pairs, and the potential to form GA, GG, or UU pairs. The database of known three‐dimensional structures allows for comparison with the models used for predicting stability from sequence. © 2001 John Wiley & Sons, Inc. Biopoly (Nucleic Acid Sci) 52: 157–167, 1999/2000

Thermodynamic examination of the pyrophosphate sensor helix in the thiamine pyrophosphate riboswitch

“…The modified 59 C48-G67 closing base pair is more stable by 0.3 kcal/mol in pH 7.5 over the wildtype construct's 59 G48-C67 closing base pair. This nearestneighbor effect is not consistent with previous studies of GdA and AdG symmetric tandem mismatches, where a G-C closing base pair is more stable than a C-G base pair (Walter et al 1994;Schroeder et al 1999;Xia et al 1999).…”

A mutate-and-map strategy accurately infers the base pairs of a 35-nucleotide model RNA

“…Similar calculations with the RNAstructure and UNAfold packages are given in Supplemental Figure S2. These calculations have limitations: They are based on modeling non-pseudoknotted configurations of base pairs; the assumed energies of single mismatches and long internal loops are based on an incomplete database of thermodynamic measurements (Kierzek et al 1999;Mathews et al 1999;Schroeder et al 1999;Hofacker 2004;Davis and Znosko 2007; and the salt conditions for the database (1 M NaCl) are different from the current experimental conditions (50 mM Na-HEPES at pH 8.0). Furthermore, uncertainties in predicting chemical modification rates from secondary structure models (as discussed in Quarrier et al 2010) preclude a fine, quantitative comparison.…”

NMR Structures of (rGCUGAGGCU)2 and (rGCGGAUGCU)2: Probing the Structural Features That Shape the Thermodynamic Stability of GA Pairs,

“…Most of this variation can be attributed to the extra hydrogen bond in each closing pair of , relative to , , and . The extra hydrogen bonds are expected to enhance stability by about 1.3 kcal/mol (19). This suggests that interactions in the internal loop differ from those in the other sheared GA structures.…”

“…Part of the ΔΔG°l oop in going from to can be parsed into a change in the number of hydrogen bonds in the closing base pairs. The average difference between closing an internal loop with two GC and two AU pairs is 1.3 kcal/mol (19) and is expected to be similar for GC to GU closure if only the number of hydrogen bonds is important. The difference in stabilities of and is consistent with this expectation.…”

“…The sequence dependence of internal loop stability and structure has been extensively studied experimentally and some computational approaches have also been tested (39)(40)(41). Despite this effort, there are many unknowns regarding the nature of the physicochemical forces shaping internal loop stability, structure, and dynamics (19,42,43). In order to gain further insight into the nature of these forces, this paper presents the solution three dimensional structures of tandem GA pairs closed by GU pairs.…”