Improved melting temperature predictions for single LNA modifications in synthetic DNA oligonucleotides

Locked nucleic acids (LNA) is a modification to DNA that generally increases the melting temperature in double strands. The nearest-neighbour (NN) provides one of the best prediction accuracies and is attractive for its simplicity. Here, we revise the NN parametrization for single LNA modifications with a very large set of published melting temperatures and using a parameter optimization method especially aimed at accurate melting temperature predictions. We show that the new set of LNA-NN parameters achieves an improved prediction of 0.88 ◦C over older parameter sets that achieve 1.7 °C for this data. We also tested if the existing salt corrections for DNA could be used for LNA as well. Using a small set of low salt melting temperatures we show that by applying the usual DNA salt corrections one may obtain predictions within an average uncertainty of 3.0 °C.