A computational model for predicting RNA nearest neighbor free energy rankings has been expanded to include the nonstandard nucleotide inosine. The model uses average fiber diffraction data and molecular dynamic simulations to generate input geometries for Quantum mechanic calculations. This resulted in calculated intrastrand stacking, interstrand stacking, and hydrogen bonding energies that were combined to give total binding energies. Total binding energies for RNA dimer duplexes containing inosine were ranked and compared to experimentally determined free energy rankings for RNA duplexes containing inosine. Statistical analysis showed significant agreement between the computationally determined rankings and the experimentally determined rankings. (C) 2015 Elsevier B.V. All rights reserved.