About the Workshop

Location: Spallation Neutron Source, ORNL

Synopsis: This meeting will bring together scientists to discuss new opportunities for biomedical research at the two advanced neutron user facilities (SNS and HFIR) at the Department of Energy’s (DOE) Oak Ridge National Laboratory (ORNL). Users now have access to some of the world’s most intense neutron beamlines for studying the structure, function, and dynamics of complex biological systems. ORNL plans to establish and operate a biomedical neutron technology research center (BNTRC) that will integrate and develop neutron scattering technologies with high performance supercomputing and biomolecular synthesis and deuterium-labeling. Participants will identify new scientific challenges and lines of biomedical inquiry that will drive the development and integration of these leading-edge technologies. An important function of the BNTRC will be to provide training, access, and expert assistance in these technologies to biomedical researchers.

In a satellite meeting, the developers of the comprehensive software suite Phenix (http://www.phenix-online.org/) for macromolecular structure determination will give a one-day workshop on the use of the software for macromolecular neutron crystallography (MNC). Participants are encouraged to bring a laptop for the afternoon tutorial session. MNC is in a period of expansion at the moment; in North America the number of beamlines suitable for MNC is expected to quadruple over the next year. This workshop will introduce current and future MNC users to the new experimental beamlines at ORNL and provide a tutorial for structure refinement using PHENIX and nCNS. New developments will be described that greatly enhance structure refinement. Participants will be given real X-ray and neutron (XN) data and will be taken through joint XN structure refinement of proteins.

Background: Neutron scattering is exquisitely sensitive to hydrogen, an atom that is ubiquitous in biological systems and that plays crucial roles in most life processes. Further, neutron scattering techniques can probe enormous ranges of length and time scales from angstroms to microns and picoseconds to milliseconds. These multiscale phenomena are intrinsic to biological processes at the molecular level and cellular levels and span from the atomic-resolution analysis of individual hydrogen atoms in proteins and nucleic acids through to meso- and macro-scale analysis of biological complexes and assemblies, biomembranes, and drug delivery systems.

ORNL operates two powerful and advanced neutron scattering research facilities, the Spallation Neutron Source (SNS) and the High Flux Isotope Reactor (HFIR), and has developed a suite of instruments that are optimized for structural biology research. Three new single crystal diffraction beam lines will enable precise location of hydrogen atoms in biomacromolecular structures and complexes, providing insights into drug and ligand binding and enzyme mechanism. Small Angle Neutron Scattering instruments probe length scales typical of supramolecular complexes and can resolve structural details of protein, nucleic acid and lipid components within functional, intact complexes under physiological conditions. These instruments are complemented by other neutron scattering instrumentation well-suited to the study of structure and dynamics in biological systems.

ORNL now plans to establish and operate a biomedical neutron technology research center (BNTRC) that will integrate and develop neutron scattering technologies with high performance supercomputing and biomolecular synthesis. The Frontiers in Neutron Structural Biology meeting will bring together leaders in biomedical and neutron scattering research to identify the driving biological problems and technology research and development (TR&D) that will be required to address the current and future needs of the biomedical research community.