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.
Furini, S., Barbini, P., Domene, C. (2013). DNA-recognition process described by MD simulations of the lactose repressor protein on a specific and a non-specific DNA sequence. NUCLEIC ACIDS RESEARCH, 41(7), 3963-3972 [10.1093/nar/gkt099].
DNA-recognition process described by MD simulations of the lactose repressor protein on a specific and a non-specific DNA sequence
FURINI, SIMONE;BARBINI, PAOLO;
2013-01-01
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.File | Dimensione | Formato | |
---|---|---|---|
NAR 2013.pdf
non disponibili
Tipologia:
Post-print
Licenza:
NON PUBBLICO - Accesso privato/ristretto
Dimensione
2.78 MB
Formato
Adobe PDF
|
2.78 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/45484
Attenzione
Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo