Thermodynamic Parameters for an Expanded Nearest-Neighbor Model for Formation of RNA Duplexes with Watson−Crick Base Pairs

TLDR

The study proposes a physical model attributing differences in duplex stability to the differential treatment of AU and GC terminal base pairs, linking hydrogen bond count to base composition. The authors derived new thermodynamic parameters from optical melting of 90 RNA duplexes and tested end/base composition effects using additional duplexes with identical nearest neighbors but varying termini. The new parameters show that terminal GC pairs confer greater stability, and applying a 0.45 kcal/mol penalty to terminal AU pairs improves ΔG°37 predictions; overall, the model predicts ΔG°, ΔH°, ΔS°, and TM within 3.2 %, 6.0 %, 6.8 %, and 1.3 °C, respectively, matching experimental limits.

Abstract

Improved thermodynamic parameters for prediction of RNA duplex formation are derived from optical melting studies of 90 oligoribonucleotide duplexes containing only Watson−Crick base pairs. To test end or base composition effects, new sets of duplexes are included that have identical nearest neighbors, but different base compositions and therefore different ends. Duplexes with terminal GC pairs are more stable than duplexes with the same nearest neighbors but terminal AU pairs. Penalizing terminal AU base pairs by 0.45 kcal/mol relative to terminal GC base pairs significantly improves predictions of ΔG°37 from a nearest-neighbor model. A physical model is suggested in which the differential treatment of AU and GC ends accounts for the dependence of the total number of Watson−Crick hydrogen bonds on the base composition of a duplex. On average, the new parameters predict ΔG°37, ΔH°, ΔS°, and T M within 3.2%, 6.0%, 6.8%, and 1.3 °C, respectively. These predictions are within the limit of the model, based on experimental results for duplexes predicted to have identical thermodynamic parameters.