Reply to “Comment on 'Computational Model for Predicting Experimental RNA and DNA Nearest-Neighbor Free Energy Rankings'”

Computational Approaches to Predicting the Impact of Novel Bases on RNA Structure and Stability

“…Although additional work will be required to make such predictions quantitatively accurate, this approach appears to have promise for the prediction of not only base-pairing partners but also stacking preferences; however, this has not been without debate. 68,69 Kamya and Muchall utilized a similar approach (X-ray crystal structure data for nucleobase geometries and the PBE0 DFT method for energy calculations, along with QTAIM 70 [Quantum Theory of Atoms In Molecules] analysis of electron density) to quantify hydrogen bonding and π-stacking interactions. 71 On the basis of their results, these researchers suggested that conflicting experimental and computational evidence on the relative strengths of A•T and A•U base pairs 64 is likely a manifestation of sequence effects, i.e., the context in which such base pairs occur can tip the balance.…”

“…Although additional work will be required to make such predictions quantitatively accurate, this approach appears to have promise for the prediction of not only base-pairing partners, but also stacking preferences, however this has not been without debate. (68, 69) …”

“…Using nucleobase geometries from average diffraction data and QM (MP2) energy calculations, these researchers were able to demonstrate a correlation between predicted and experimental nearest-neighbor binding energies. Although additional work will be required to make such predictions quantitatively accurate, this approach appears to have promise for the prediction of not only base-pairing partners but also stacking preferences; however, this has not been without debate. , …”

A computational model for predicting experimental RNA nearest-neighbor free energy rankings: Inosine·uridine pairs

“…1–4 The study computationally determined energies for all standard nucleotide combinations and successfully compared these computational rankings to experimentally determined nearest neighbor (NN) free energy rankings. 1,5,6 The method resulted in rankings that agreed well with the experimental rankings, but it has not been tested on non-Watson-Crick pairs.…”