Studying Nucleic Acid-Ligand Binding by X-Ray Crystallography

The technique of X-ray crystallography is over a hundred years old and has been applied to the study of nucleic acids since the 1980s. Since that time, this method has provided the fundamental details of nucleic acid structure, starting with the DNA double helix, and now extending to encompass the diversity of both DNA and RNA and their interactions with both small molecules (ligands) and proteins. The technique generates primary structural data used in computational studies, drug design, and anyone needing to understand nucleic acids at the molecular level. Both in the generation of suitable crystals and in the procedures used for measurements and data analysis, there are many ways in which the wider area of macromolecular crystallography has provided essential tools, which in turn have been adapted to the description of nucleic acids. The validation tools provided by the structural databanks mean that the reliability of the data and final model can be assessed against standard criteria and benchmarks. The data is then in the public domain and can be accessed freely worldwide, an important contribution to international scholarship. In this chapter, we explain these crystallographic methods applied to DNA structures containing bound ligands, together with some illustrative examples.