Institution: | a Department of Physical Chemistry and Mathematics, Facultad de Química, Universidad de la República, 11800 Montevideo, Uruguay b Cátedra de Biología, Facultad de Química, Universidad de la República, 11800 Montevideo, Uruguay c Institut de Génétique et Microbiologie, UMR CNRS C8621, Université Paris Sud XI, Bâtiment 409, Centre d'Orsay, 91405 Orsay cedex, France d Department of Physical Chemistry, Uppsala University, P.O. Box 532, S-75121 Uppsala, Sweden |
Abstract: | CreA, the negative regulator mediating carbon catabolism repression in Aspergillus nidulans, is a protein that contains a DNA-binding domain comprising two zinc finger motifs. A 3D model for the CreA–G4 (5′-GCGGGGGCGT-3′) complex is constructed on the basis of the structure of the Zif268–DNA crystal complex Science 252 (1991) 809] and using similarity analysis and computer assisted modelling techniques. The CreA–G4 model was then subjected to a set of molecular dynamics (MD) studies. Based on our previous nano second long Zif268–DNA MD simulation, a 170 ps long trajectory was deemed sufficient to test possible DNA–protein interactions. A screening of the static model and of the trajectory was performed for protein amino acids, nucleotide bases, phosphates backbone and water molecules mediating protein–DNA contacts. Energy, root mean square deviation (RMSD), principal inertial moment and distances were analysed. For this time span, the stability shown in fluctuation patterns reveals the presence of a complex behaving in a manner similar to Zif268–DNA. An unambiguous characterisation of the amino acids involved in DNA-binding was obtained. These results could contribute towards the establishment of a code of protein–DNA recognition for this class of DNA-binding motifs. |