X-ray crystallography at subatomic resolution

Abstract

The diffraction of X-rays by molecular crystals is the technique of reference for obtaining three-dimensional information about atomic positions and interactions, information essential for the comprehension of the function and the molecular mechanisms. In the case of small molecules, very precise high resolution measurements allowed the observation of hydrogen atoms of and bond electronic densities. Thus, relations could be established between the deviations from standard stereochemistry of spherical atomic models and the chemical reactivity. In the case of biological macromolecules, one could correlate the spatial arrangement of the components of proteins and nucleic acids to their biological function. These two types of studies progressed independently during the two last decades, primarily because of the limited resolution of the macromolecular crystallographic results, 2 to 3 Å in the majority of the cases, against 0.5 Å or better for the small molecules. The resolution, which is the minimal separation of the crystal plans giving place to an observable X-ray diffraction spot, is indeed an essential parameter of a crystallographic study. It is directly related to the minimum distance separating the details of the electronic density. A resolution of 2 Å is sufficient to distinguish peptides from a protein or the bases of a nucleic acid, but not the individual atoms, and even less the bond densities.