Locating Hydrogen Atoms in a Protein Using Neutron Crystallography


Hydrogen atoms are notoriously difficult to locate in proteins, yet they are key atoms in many of the chemical reactions of life and comprise one-half of a protein’s atoms. X-ray crystallography has been used to determine the atomic structure of many proteins and macromolecular complexes, but only a small fraction of the hydrogen atoms in these molecules can be located using this technique. In contrast, neutrons are scattered by hydrogen atoms, enabling determination of the position of these atoms in a protein molecule, though usually only to a medium resolution of about 2Å. Now, scientists at the Los Alamos Neutron Science Center have used the Protein Crystallography Station to determine the structure of a protein with the positions of its hydrogen atoms defined to an ultrahigh resolution of 1.1Å, the highest resolution ever for a neutron structure of a protein. They were able not only to locate nearly 95% of the hydrogen atoms in the protein at this resolution, but could determine the location of the hydrogen bonds that help determine the three-dimensional structure of the folded protein, and in some cases see how individual hydrogen atoms vibrate about their position in the protein. This new capability will improve understanding of the activity of many proteins, as well as guide computational modeling of systems such as protein-substrate and protein-drug complexes. The research was a collaboration of scientists at the University of Toledo, Los Alamos National Laboratory, and Oak Ridge National Laboratory.


Chen, J. C.-H., B.L. Hanson, S.Z. Fisher, P. Langan, and A.Y. Kovalevsky. 2012. “Direct Observation of Hydrogen Atom Dynamics and Interactions by Ultrahigh Resolution Neutron Protein Crystallography,” Proceedings of the National Academy of Sciences (USA) 109(38), 15301–306. DOI: 10.1073/pnas.1208341109.