DNA simulation benchmarks as revealed by X-ray structures

The inferences that can be drawn from known DNA structures provide new stimuli for improvement of nucleic acid force fields and fresh ideas for exploration of the sequence-dependent properties of DNA. The rapidly growing database of high-resolution nucleic acid crystal structures reveals long anticipated sequence-dependent variability in DNA backbone conformation. Nucleotides in specific sequence contexts exhibit decided tendencies to undergo changes of rotational state that are associated with large-scale helical transitions. In particular, the sugars attached to cytosine exhibit a clear-cut tendency to adopt A-like conformations. Overall, however, the large set of protein-bound DNA structures remains very close to the classical B form. This distinguishes the crystallographically observed DNA duplexes from computergenerated atomic-level DNA models, which are characterized by a systematic shift toward the A form. In addition, the base-pair steps found in different protein-DNA complexes span a narrower range of conformational states than those generated with state-of-the-art molecular simulations. The sequencedependent positioning of water and the build-up of amino acid residues around the DNA bases point to mechanisms which may underlie the sequencedependent structure and deformability of DNA in complexes with ligands.