Conformational study on the interaction between DNA and protein

Abstract

The conformational analysis of dinucleotide dGpdCp and tetrapeptide β-alanine to the complex has been carried out using an empirical potential function, varying all the independent degrees of freedom of the DNA and protein backbones. To understand the factors involved in the change of one conformation to another, the configurational entropies of the conformer and water molecules bound to it have been estimated by using a potential surface analysis method. The total free energy changes for each conformational transition between dinucleotide, tetrapeptide, and their complex at room temperature were calculated and compared with each other. The free energy change of the free DNA and β-alanine to the free complex is -70.0 kcal/mole, in which the interaction energy change is -49.5 kcal/mole and the entropy change is 68.9 e.u.. Through the hydration, there have been large changes of free energies: -664.0 kcal/mole for DNA, -72.0 kcal/mole for β-alanine, and -682.3 kcal/mole for the complex. The entropy changes corresponding to them are -28.1, -48.3, and -178.5 e.u., respectively. The free energy change of the hydrated DNA and β-alanine to the hydrated complex is -16.2 kcal/mole, in which the energy change is -26.1 kcal/mole and the entropy change is -33.2 e.u.. It is found from analyzing the interaction energies that the entropy change is mainly caused by the conformational entropy change of DNA and protein through the complex formation and that the major contribution to the total interaction energy is ascribed to the hydrogen bond between the conformer and water molecules bound to it. Whereas the hydration including counterions and bound water molecules is proved to paly an important role in determining the conformational stability of DNA, protein, and their complex.