On the complementarity of X-ray and NMR data

X-ray crystallography and NMR contain complementary information for the characterization of biological macromolecules. X-ray diffraction is primarily sensitive to the overall shape of the molecule, and can progress towards the atomic detail as the number and quality of the reflections is increased; on the contrary, whereas NMR is mostly sensitive to the atomic detail and is able to progress to longer range for increased number of restraints. Their combination can therefore provide a stronger justification for the resulting structure. For their combination we have recently proposed REFMAC-NMR, which relies on primary data from both techniques for joint refinement. This possibility raises the compelling question of how far the complementarity can be extended. In this paper, we describe the joint refinement of four X-ray structures of hen-egg-white lysozyme, solved at atomic resolution in four different crystal forms, and we demonstrate that the outcome critically depends on the crystal form itself, reflecting the sensitivity of NMR to fine details.