DNA simulation benchmarks as revealed by X-ray structures

Abstract

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. © 2006 Springer.