Changes in thermodynamic properties of DNA base pairs in protein-DNA recognition.

The mechanism of protein-DNA recognition, particularly the induced fit mechanism, is poorly understood due to ineffective analysis of the protein-DNA complex crystal structures. It is expected that upon protein binding the DNA becomes structurally more rigid. However, a previous analysis (W.K. Olson, A. A. Gorin, X. Lu, L. M. Hock and V. Zhurkin,Proc. Natl. Acad. Sci. USA, 95, 11163 (1998)) indicates increase in the flexibility of the DNA segment complexed with protein. We have considered an ensemble of configurations from crystallographic data of the TBP-TATA box complex structures under a given thermodynamic condition. Analysis of the ensemble of structures of this complex indicates that the DNA deforms significantly to form specific hydrogen bonds and as a consequence, its structure attains more rigidity. We calculate the free energy profiles in term of the DNA base pair (bp) step parameters via the binding patterns in the ensemble of the given complex, and for free DNA bp steps as well. The rigidities estimated from these free energies for small deformations around the minimum indicate enhanced structural rigidities of DNA upon complexation with protein. Further, the changes in the thermodynamic properties of the bp steps upon complex formation have been estimated from the two sets of free energy profiles. These results indicate differential role played by different bp steps in the thermodynamic stabilization of the complex.