Recognition determinants in a T4 ← G4 mutant derived from a 5′-GCGTGGGCGT-3′ oligomer in a zinc finger 268-DNA complex.: A molecular dynamics study of the fully charged complex in water

The 5'-GCGTGGGCGT-3' (T4) oligomer found in the zinc finger 268-DNA complex was mutated into the sequence 5'-GCGGGGGCGT-3' (G4). A 3D model was constructed from the T4 sequence using an X-ray structure as a template. Molecular dynamics simulations were used to test the thermal stability of the model. A 500-ps trajectory was obtained for the fully charged complex in water using GROMOS87. The complex and the G4 sequence are found to have dynamically stationary behavior. Comparisons made with a previous T4 sequence molecular dynamics simulation show both systems have similar thermal stability. The structure of DNA appears to be maintained by its global interactions with the protein although the mutated site does not contribute with its full potential for binding. The protein structure shows some small differences compared to the T4 simulation. The simulation provided evidence for the role of a chloride ion interacting with the protein and helping in the recognition process.