<P> In the third step, these data are combined computationally with complementary chemical information to produce and refine a model of the arrangement of atoms within the crystal . The final, refined model of the atomic arrangement--now called a crystal structure--is usually stored in a public database . </P> <P> As the crystal's repeating unit, its unit cell, becomes larger and more complex, the atomic - level picture provided by X-ray crystallography becomes less well - resolved (more "fuzzy") for a given number of observed reflections . Two limiting cases of X-ray crystallography--"small - molecule" (which includes continuous inorganic solids) and "macromolecular" crystallography--are often discerned . Small - molecule crystallography typically involves crystals with fewer than 100 atoms in their asymmetric unit; such crystal structures are usually so well resolved that the atoms can be discerned as isolated "blobs" of electron density . By contrast, macromolecular crystallography often involves tens of thousands of atoms in the unit cell . Such crystal structures are generally less well - resolved (more "smeared out"); the atoms and chemical bonds appear as tubes of electron density, rather than as isolated atoms . In general, small molecules are also easier to crystallize than macromolecules; however, X-ray crystallography has proven possible even for viruses and proteins with hundreds of thousands of atoms, through improved crystallographic imaging and technology . Though normally X-ray crystallography can only be performed if the sample is in crystal form, new research has been done into sampling non-crystalline forms of samples . </P> <P> Although crystallography can be used to characterize the disorder in an impure or irregular crystal, crystallography generally requires a pure crystal of high regularity to solve the structure of a complicated arrangement of atoms . Pure, regular crystals can sometimes be obtained from natural or synthetic materials, such as samples of metals, minerals or other macroscopic materials . The regularity of such crystals can sometimes be improved with macromolecular crystal annealing and other methods . However, in many cases, obtaining a diffraction - quality crystal is the chief barrier to solving its atomic - resolution structure . </P> <P> Small - molecule and macromolecular crystallography differ in the range of possible techniques used to produce diffraction - quality crystals . Small molecules generally have few degrees of conformational freedom, and may be crystallized by a wide range of methods, such as chemical vapor deposition and recrystallization . By contrast, macromolecules generally have many degrees of freedom and their crystallization must be carried out so as to maintain a stable structure . For example, proteins and larger RNA molecules cannot be crystallized if their tertiary structure has been unfolded; therefore, the range of crystallization conditions is restricted to solution conditions in which such molecules remain folded . </P>

Who used experimental techniques to look at dna techniques like x-ray crystallography