DNA-Binding Proteins

The lactose operon was first described in the late 60's by the classical studies of Jacob & Monod.  Nowadays the lactose repressor, LacI, is one of the best characterized DNA-binding proteins, which makes it the ideal system for studying the DNA recognition process by numerical simulations.

Furini S & Domene C, J Phys Chem B, 2014

With a combination of umbrella sampling and metadynamics simulations we revealed that when aligned with a specific sequence, LacI establishes polar interactions with the base edges that require ∼4 kcal/mol to be disrupted. In contrast, these interactions are not stable when the protein is aligned with nonspecific sequences. These results confirm that LacI is able to efficiently recognize a specific sequence while sliding along DNA before any structural change of the protein–DNA complex occurs.

DNA-recognition process described by MD simulations of the lactose repressor protein on a specific and a non-specific DNA sequence

Furini S, Barbini P. & Domene C., Nucl Acids Res, 2013

We simulated the dynamics of the lactose repressor on a specific and a non-specific DNA sequence. When aligned with nonspecific DNA the protein was as mobile as when free in solution, while binding to a specific sequence causes a drastic reduction in protein mobility. The entropic and enthalpic contribution to the binding energy are analyzed by an MM-PBSA approach.

Insights into the Sliding Movement of the Lac Repressor Nonspecifically Bound to DNA

Furini S., Domene C. & Cavalcanti S., J Phys Chem B, 2010

The lactose repressor finds its DNA binding sequence faster than what expected from a 3-dimensional Brownian motion. This is possible thanks to 1-dimensional rapid movements along the DNA molecule. In this paper we analyze the sliding movement of LacI along an helical trajectory around a DNA molecule with a non-specific sequence.