Dynamics and thermodynamics of water around EcoRI bound to a minimally mutated DNA chain.

Water plays an important role in protein-DNA interactions. Here, we examine using molecular dynamics simulations the differences in the dynamic and thermodynamic properties of water in the interfacial and intercalating regions of EcoRI bound to the cognate and to a minimally mutated noncognate DNA chain. The results show that the noncognate complex is not only more hydrated than the cognate complex, but the interfacial waters in the noncognate complex exhibit a faster dynamics, which in turn reduces the hydrogen-bond lifetimes. Thus, the higher hydration, faster reorientation dynamics and faster hydrogen-bond-relaxation times of water, taken together, indicate that, even with a minimal mutation of the DNA sequence, the interfacial regions of the noncognate complex are more poised to allowing the protein to diffuse away than to promoting the formation of a stable complex. Alternatively, the results imply that the slowed water dynamics in the interfacial regions when the protein chances upon a cognate sequence allow the formation of a stable specific protein-DNA complex leading to catalytic action.