Heterogeneous Dynamical Environment at the Interface of a Protein-DNA Complex

Binding between protein and DNA is an essential process to regulate different biological activities. Two puzzling questions in protein-DNA recognition are (i) how the protein's binding domain identifies the DNA sequence in an aqueous solution and (ii) how the formation of the complex alters the dynamical environment around it. In this work, we present results obtained from molecular dynamics simulations of the N-terminal α-helical domain of the λ-repressor protein (in dimeric form) bound to the corresponding operator DNA. Effects of formation of the complex in modifying the microscopic dynamics of water as well as the kinetics of hydrogen bonds at the interface have been explored. Locally heterogeneous restricted water motions at the complex interface have been observed, the extent of restriction being more significant around the directly bound residues of the protein and the DNA. In particular, the calculation revealed the existence of significantly constrained motionally restricted water layer that can form either bridges around the directly bound residues of the protein and DNA or are engaged in forming water-mediated contacts between a fraction of the unbound residues. More importantly, it is observed that the restricted water motion around the complex is correlated with the hydrogen bond relaxation time scale at the interface. It is further demonstrated that the kinetics of water-water hydrogen bonds involving the bridged water are influenced more due to complex formation.