Flexibility of the Binding Regions of a Protein-DNA Complex and the Structure and Ordering of Interfacial Water

Noncovalent interactions between protein and DNA are important to comprehend different biological activities in living organisms. One important issue is how the protein identifies the target DNA and the influence of the resulting protein-DNA complex on the hydration environment around it. In this study, we have carried out atomistic molecular dynamics simulations of the protein-DNA complex formed by the dimeric form of the α-helical N-terminal domain of the λ-repressor protein with its operator DNA. Local heterogeneous flexibilities of the residues of the protein and the DNA components that are involved in binding and the microscopic structure and ordering of water around those have been investigated in detail. The calculations revealed concurrent existence of highly ordered as well as disordered water molecules at the interface. It is found that a fraction of doubly coordinated water molecules exhibit high degree of ordering at the interface, while the randomly oriented ones are coordinated with three water molecules. The effect has been found to be more around the protein and DNA residues that are in contact in the complexed state. We believe that such highly ordered two-coordinated water molecules are likely to act as an adhesive to facilitate the formation of a protein-DNA complex and maintain its structural stability.