The ability to accurately predict the 3D structure of RNA relies upon an in-depth model that accounts for unique structural motifs in the secondary and tertiary structure. Current algorithms utilize the free energy of nearest neighbors to calculate the secondary structure based on sequence. Dinucleotide bulges in RNA are one structure that is commonly found in nature, yet there is little data concerning their thermodynamic parameters. Current models assign a free energy penalty of 2.8 kcal/mol for all dinucleotide bulges, regardless of their sequence. Short RNA duplexes containing dinucleotide bulges of different sequences and with different nearest neighbor combinations were optically melted. From these melts their thermodynamic parameters (enthalpy, entropy, Gibb’s free energy, and melting temperature) were determined. This thermodynamic data was utilized to create an updated model to predict the free energy contribution of dinucleotide bulges. This sequence dependent model assigns free energy penalties based on the sequence composition of the bulging nucleotides (two purines, two pyrimidines, or one of each). The predictive model also includes a penalty for an A-U pair and a bonus for G-U pair adjacent to the bulge. The new sequent dependent model results in predicted values that are within 0.18 kcal/mol of the experimental values; a significant improvement over the sequence independent model. This new experimental data and updated sequence dependent model can be utilized by algorithms that predict RNA free energies as well as those that use free energy minimization to predict RNA secondary structure from sequence.

Improved model to predict the free energy contribution of dinucleotide bulges to RNA duplex stability

249th National Meeting (2015)

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