Molecular dynamics studies on free and bound targets of the Bovine Papillomavirus type I E2 protein : the protein binding effect on DNA and the recognition mechanism

¹ IBPC

^* To whom correspondence should be addressed. E-mail: dragana.djuranovic{at}univ-paris5.fr.

Submitted on November 26, 2004
Revised on February 7, 2005
Accepted on 8 June 2005

	Abstract

Molecular dynamics simulations of a total duration of 30ns in explicit solvent were carried out on the BPV-1-E2 protein complexed to a high affinity DNA target containing the two hydrogen bounded ACCG.CGGT half-sites separated by the non-contacted ACGT sequence. The analysis of the trajectories focuses on the DNA structure and on the dynamics. The data are compared to those issued from recent simulations made on three free targets that recognize E2 with different affinities (Djuranovic et al., 2004). E2 does not drastically perturb the mechanic properties of the free DNA: the structural relationships between the BI/BII backbone sub-states and some helical parameters are preserved in the complex despite of a severe slowing down of the phosphate group motions. The structures of both free and bound half-sites are very close to each other although the conformational space explored by these regions is narrowed when they are contacted by the protein. The enhanced plasticity found in the best free target spacers, mainly manifest through the backbone motions, allows a clear overlap between several free and bound global DNA features such as the base displacement. Furthermore, this flexibility is preserved in the complex. Our results support the hypothesis that E2 takes advantage of free pre-distorted structures that may minimize the DNA deformation cost. In addition, we observe that E2 is far from totally stiffening the DNA, suggesting that the entropic penalty inherent to the complex formation could be limited.

Key Words: BPV-1-E2, DNA dynamics, E2-E2BS, molecular dynamics, protein-DNA complex, protein-DNA specific recognition

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