Predicting DNA Duplex Stability from the Base Sequence

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 (Δ G⚬) and the melting behavior (Δ H⚬) of any DNA duplex structure from inspection of its primary sequence. This capability should prove valuable in numerous applications, such as (i) predicting the stability of a probe--gene complex; (ii) selecting optimal conditions for a hybridization experiment; (iii) deciding on the minimum length of a probe; (iv) predicting the influence of a specific transversion or transition on the stability of an affected DNA region; and (v) predicting the relative stabilities of local domains within a DNA duplex.