Influence of DNA stiffness in protein-DNA recognition

Protein-DNA recognition plays an essential role in the regulation of gene expression. The protein-DNA binding specificity is based on direct atomic contacts between protein and DNA and/or the conformational properties of DNA. In this work, we have analyzed the influence of DNA stiffness (E) to the specificity of protein-DNA complexes. The average DNA stiffness parameters for several protein-DNA complexes have been computed using the structure based sequence dependent stiffness scale. The relationship between DNA stiffness and experimental protein-DNA binding specificity has been brought out. We have investigated the importance of DNA stiffness with the aid of experimental free energy changes (Delta Delta G) due to binding in several protein-DNA complexes, such as, ETS proteins, 434, lambda, Mnt and trp repressors, 434 cro protein, EcoRV endonuclease V and zinc fingers. We found a correlation in the range 0.65-0.97 between Delta Delta G and E in these examples. Further, we have qualitatively analyzed the effect of mutations in the target sequence of. repressor and we observed that the DNA stiffness could correctly identify 70% of the correct bases among the considered nine positions. (c) 2005 Elsevier B.V. All rights reserved.