title: DNA-recognition process described by MD simulations of the lactose repressor protein on a specific and a non-specific DNA sequence.
abstract: The lactose repressor protein may bind DNA in two possible configurations: a specific one, if the DNA sequence corresponds to a binding site, and a non-specific one otherwise. To find its target sequences, the lactose repressor first binds non-specifically to DNA, and subsequently, it rapidly searches for a binding site. Atomic structures of non-specific and specific complexes are available from crystallographic and nuclear magnetic resonance experiments. However, what remains unknown is a detailed description of the steps that transform the non-specific complex into the specific one. Here, how the protein first recognizes its binding site has been studied using molecular dynamics simulations. The picture that emerges is that of a protein that is as mobile when interacting with non-specific DNA sequences as when free in solution. This high degree of mobility allows the protein to rapidly sample different DNA sequences. In contrast, when the protein encounters a binding site, the configuration ensemble collapses, and the protein sliding movements along the DNA sequence become scarce. The binding energies in the specific and non-specific complexes were analysed using the Molecular Mechanics Poisson Boltzmann Surface Area approach. These results represent a first step towards a throughout characterization of the DNA-recognition process.
authors: Department of Medical Biotechnology, University of Siena, viale Mario Bracci 12, I-53100 Siena, Italy. simone.furini@unisi.it
authors: Simone
authors: S
authors: Furini
authors: Paolo
authors: P
authors: Barbini
authors: Carmen
authors: C
authors: Domene
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012097:Repressor Proteins; D004247:DNA