A method for determining atomic level structures of macromolecule-ligand
complexes through high-resolution powder diffraction analysis and a
method for providing suitable microcrystalline powder for diffraction
analysis are provided. In one embodiment, powder diffraction data is
collected from samples of polycrystalline macromolecule and
macromolecule-ligand complex and the refined structure of the
macromolecule is used as an approximate model for a combined Rietveld and
stereochemical restraint refinement of the macromolecule-ligand complex.
A difference Fourier map is calculated and the ligand position and points
of interaction between the atoms of the macromolecule and the atoms of
the ligand can be deduced and visualized. A suitable polycrystalline
sample of macromolecule-ligand complex can be produced by physically
agitating a mixture of lyophilized macromolecule, ligand and a solvent.