Predicting DNA duplex stability from the base sequence.

TLDR

The authors present a complete thermodynamic library of all ten Watson‑Crick DNA nearest‑neighbor interactions and demonstrate how it can be used to predict the stability and temperature‑dependent behavior of any DNA duplex from its base sequence. They derived the data from calorimetric studies on 19 DNA oligomers and 9 polymers and applied the nearest‑neighbor model to calculate transition enthalpies and free energies for test oligomers. The calculated values agree excellently with experimental measurements, confirming that duplex thermodynamics are additive and enabling accurate prediction of melting behavior for diverse applications.

Abstract

We report the complete thermodynamic library of all 10 Watson-Crick DNA nearest-neighbor interactions. We obtained the relevant thermodynamic data from calorimetric studies on 19 DNA oligomers and 9 DNA polymers. We show how these thermodynamic data can be used to calculate the stability and predict the temperature-dependent behavior of any DNA duplex structure from knowledge of its base sequence. We illustrate our method of calculation by using the nearest-neighbor data to predict transition enthalpies and free energies for a series of DNA oligomers. These predicted values are in excellent agreement with the corresponding values determined experimentally. This agreement demonstrates that a DNA duplex structure thermodynamically can be considered to be the sum of its nearest-neighbor interactions. Armed with this knowledge and the nearest-neighbor thermodynamic data reported here, scientists now will be able to predict the stability (delta G degree) and the melting behavior (delta H degree) of any DNA duplex structure from inspection of its primary sequence. This capability should prove valuable in numerous applications, such as predicting the stability of a probe-gene complex; selecting optimal conditions for a hybridization experiment; deciding on the minimum length of a probe; predicting the influence of a specific transversion or transition on the stability of an affected DNA region; and predicting the relative stabilities of local domains within a DNA duplex.