Sequence-dependent dynamics of TATA-Box binding sites.

We have carried out two nanosecond-length molecular dynamics simulations on a DNA oligomer, d(GCGTAAAAAAAACGC)2, which contains a weak binding site for the TATA-box binding protein. An analysis of the resulting trajectories shows that this oligomer behaves differently from a related oligomer [d(GCGTATATAAAACGC)2] studied earlier using the same protocol (Flatters, D., M. Young, D. L. Beveridge, and R. Lavery. 1997. Conformational properties of the TATA-box binding sequence of DNA. J. Biomol. Struct. & Dyn. 14:757-765), and which contains a strong binding site for the same protein. The two basepair mutations that relate these oligomers lead to significant changes in time-averaged structure and in dynamic behavior, which extend over entire length of the oligomer and appear to be compatible with the experimentally observed decrease of binding and functional activity. These results suggest that molecular dynamics simulations, taking into account explicit solvent and counterions, and avoiding the truncation of electrostatic interactions, are a powerful tool for investigating the indirect aspects of protein-nucleic acid recognition.