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 (AG') and the melting behavior (AW) 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.It is well established that under a given set of solution conditions the relative stability of a DNA duplex structure depends on its base sequence (1-4). More specifically, the stability of a DNA duplex appears to depend primarily on the identity of the nearest-neighbor bases. Ten different nearestneighbor interactions are possible in any Watson-Crick DNA duplex structure. These pairwise interactions are AA/TT; AT/TA; TA/AT; CA/GT; GT/CA; CT/GA; GA/CT; CG/GC; GC/CG; GG/CC. The overall stability and the melting behavior of any DNA duplex structure can be predicted from its primary sequence if one knows the relative stability (AG') and the temperature-dependent behavior (Al?, ACp°) of each DNA nearest-neighbor interaction (5, 6).Tinoco and coworkers already have demonstrated the power of this predictive ability with RNA molecules for which they and others have determined the appropriate thermodynamic data (7-11). Unfortunately, comparatively few corresponding studies on DNA oligomers have been performed so that the relevant thermodynamic data required to predict DNA structural stability are rather sparse. The seriousness of this deficiency is dramatized by the fact that investigators attempting to evaluate sequence-dependent structural preferences in DNA molecules have resorted to the use of the more available RNA thermodynamic data. This use of RNA data does not reflect a belief that DNA and RNA are thermodynamically equivalent but rather is born of necessity due to a lack of the relevant DNA thermodynamic data. In fact, available comparisons su...

SynopsisIn this paper, we derive the general forms of the equations required to extract thermodynamic data from equilibrium transition curves on oligomeric and polymeric nucleic acids of any molecularity. Significantly, since the equations and protocols are general, they also can be used to characterize thermodynamically equilibrium processes in systems other than nucleic acids. We briefly review how the reduced forms of the general equations have been used by many investigators to evaluate mono-and bimolecular transitions, and then explain how these equations can be generalized to calculate thermodynamic parameters from common experimental obsenrables for tramitions of higher molecularities. We emphasize the strengths and weaknesses of each method of data analysis 80 that investigators can select the approach most appropriate for their experimental c i r~c e s .We also describe how to analyze calorimetric heat capacity curvee and noncalorimetric Merentiated melting curves 80 as to extract both model-independent and model-dependent thermodynamic data for transitions of any molecularity. The general equations and methods of analysis described in this paper should be of particular interest to laboratoria that currently are investigating association and dissociation processes in nucleic acids that exhibit molecularitiea greater than two.

No abstract

No abstract

We present a comparative study of calorimetrically derived thermodynamic proffles for the binding of a series of drugs with selected DNA poly[d(A-T)]-poly[d(A-T)] behaves thermody-namically as the more "normal" host duplex toward drug binding, whereas the entropy-driven binding to the poly(dA)-poly(dT) duplex represents "aberrant" behavior. Furthermore, since each of the four drugs exhibits different modes of DNA binding, we conclude that the observed entropy-driven behavior for binding to poly(dA)-poly(dT) reflects an intrinsic property of the homopolymer duplex that is perturbed in a common manner upon ligation rather than a common property of all four binding ligands. To rationalize the large positive entropy changes that drive drug complexation with the poly-(dA)-poly(dT) duplex, we propose a model that emphasizes binding-induced perturbations of the more highly hydrated, altered B conformation of the homopolymer. Our results suggest that an aberrant thermodynamic binding proffle may reflect an unusual DNA conformation in the host duplex. However, before such a conclusion can be reached, complete