title: Interaction identification of Zif268 and TATA(ZF) proteins with GC-/AT-rich DNA sequence: A theoretical study.
abstract: Molecular dynamics (MD) simulations for Zif268 (a zinc-finger-protein binding specifically to the GC-rich DNA)-d(A(1) G(2) C(3) G(4) T(5) G(6) G(7) G(8) C(9) A(10) C(11) )(2) and TATA(ZF) (a zinc-finger-protein recognizing the AT-rich DNA)-d(A(1) C(2) G(3) C(4) T(5) A(6) T(7) A(8) A(9) A(10) A(11) G(12) G(13) )(2) complexes have been performed for investigating the DNA binding affinities and specific recognitions of zinc fingers to GC-rich and AT-rich DNA sequences. The binding free energies for the two systems have been further analyzed by using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The calculations of the binding free energies reveal that the affinity energy of Zif268-DNA complex is larger than that of TATA(ZF) -DNA one. The affinity between the zinc-finger-protein and DNA is mainly driven by more favorable van-der-Waals and nonpolar/solvation interactions in both complexes. However, the affinity energy difference of the two binding systems is mainly caused by the difference of van-der-Waals interactions and entropy components. The decomposition analysis of MM-PBSA free energies on each residue of the proteins predicts that the interactions between the residues with the positive charges and DNA favor the binding process; while the interactions between the residues with the negative charges and DNA behave in the opposite way. The interhydrogen-bonds at the protein-DNA interface and the induced intrafinger hydrogen bonds between the residues of protein for the Zif268-DNA complex have been identified at some key contact sites. However, only the interhydrogen-bonds between the residues of protein and DNA for TATA(ZF) -DNA complex have been found. The interactions of hydrogen-bonds, electrostatistics and van-der-Waals type at some new contact sites have been identified. Moreover, the recognition characteristics of the two studied zinc-finger-proteins have also been discussed.
authors.affiliation: College of Chemistry, Beijing Normal University, Beijing 100875, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Guangju
authors.initials: G
authors.lastname: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D016385:TATA Box; D013816:Thermodynamics; D016335:Zinc Fingers
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D004247:DNA