Neutron protein crystallography (nPX) more completely defines biological structures, by including hydrogen and hydration details, and thus helps explain important biomolecular functions, as exemplified by studies of aspartic proteinases, concanavalin A and rubredoxin. Furthermore, comparisons of ultra-high resolution synchrotron X-ray and nPX studies of concanavalin A show that the neutron approach is capable of delivering many more bound water details at medium diffraction resolutions (~2.4 Å) and at room temperature, which is physiologically relevant. The LMX instrument on ISIS TS2 will bring a second instrument to Europe, besides LADI at the ILL, suitable for single crystal neutron diffraction from biological macromolecules. At PCS at LANSCE, an instrument similar to LMX but with lower brilliance, 50kDa in the asymmetric unit is within reach (indeed promising data from a 220kDa protein have been reported). There is also fresh impetus from associated deuteration laboratories; samples from the new biological perdeuteration facility (D-LAB) have produced significant increase in capability from LADI, particularly from small samples. Taken together these new results tell us that the molecular weight ceiling we can expect to study with nPX on LMX will cover much of the molecular weight histogram of genomes including the multi-macromolecular complexes and molecular machines where further Nobel prizes must surely lie.
Biomolecular science also encompasses liganding small molecules, on their own as well as complexed with protein receptors. The study of these is a major interest of pharmaceutical protein crystallographers engaged in new drug discovery. Typically hundreds of such complexes are surveyed at SR X-ray beamlines. This sort of work can be expected to spin into nPX use of LMX. The nPX results from LMX will contribute to fundamental knowledge of biology at the molecular level and hence inform new biotechnologies.