Conference on New Frontiers in
Neutron Macromolecular Crystallography

July 12-13, 2005
Spallation Neutron Source
Oak Ridge National Laboratory, Oak Ridge, TN, USA

Investigating catalysis in enzyme cyclophilin A, Courtesy P Agarwal, ORNL

The advent of the Spallation Neutron Source (SNS) with over an order of magnitude increase in neutron flux, in combination with advances in neutron optics and detectors, structural genomics, and protein deuteration, will provide a new and exciting opportunity for NMC to become a routine and essential structural tool for enzymology, structural biology and functional genomics. In order to satisfy the needs of the structural biology community, a dedicated, best-in-class high-resolution time-of-flight single crystal macromolecular neutron diffractometer (MaNDi) has been proposed to be constructed at the SNS. Based on input from the structural biology community acquired over the past two years, an optimized instrument design was developed that will enable data collection rates over 50 times faster than existing facilities. Furthermore, it will enable studies of crystals with lattice constants substantially larger than currently possible with the existing facilities. It is expected that the unprecedented speed and resolution limits achievable with MaNDi for NMC experiments will greatly advance the fields of structural biology, enzymology, and computational chemistry.

Visualising hydrogen atoms in Rubredoxin (Kurihara et al., PNAS 101,11215, 2004).

Objectives

• Increase interest and awareness of the important challenges in structural biology that can be addressed by neutron diffraction;
• Discuss the exciting opportunities and funding strategies for the development of a powerful instrument (MaNDi) for high resolution neutron macromolecular crystallography with structural biologists, enzymologists, computational chemists, and scientists from the universities, national laboratories and pharmaceutical companies, as well as program managers from the funding agencies; and
• Showcase via invited talks and a poster session the novel and interesting macromolecular systems that will be amenable to neutron diffraction studies upon completion of MaNDI.

Expected outcomes

Protonation states in an aspartate proteinase-inhibitor complex, Courtesy J Cooper & L. Coates, Uni Southampton

• Enhance interest in Neutron Macromolecular Crystallography among prominent scientific leaders in structural biology research whose endorsement and support will increase the visibility of this technique at national and international levels;
• Identify important forefront macromolecular systems whose function mechanisms will greatly benefit from the unique structural information provided by Neutron Macromolecular Crystallography; and
• Develop a strong plan, including individual roles and responsibilities for MaNDi to work towards securing timely funding for the design and construction of MaNDi and related SNS infrastructure.

Confirmed speakers

• Jenny Glusker, Fox Chase Cancer Center
• Herbert A. Hauptman, Hauptman-Woodward Medical Research Institute
• Wayne Hendrickson, Columbia University
• Andrzej Joachimiak, Argonne National Laboratory
• Anthony Kossiakoff, University of Chicago
• Brian Mathews, University of Oregon
• Alberto Podjarny, IGBMC, Strasbourg, France
• Dagmar Ringe, Brandeis University
• Gerald Stubbs, Vanderbilt University
• B.C. Wang, University of Georgia

A poster session was held on Tuesday evening from 5:30 to 7:00 p.m. Poster winners were Brad Bennett for presenting results that utilized neutron diffraction and Zoe Fisher for the proposed concept of neutron use to further her research.

Poster Session Winner Brad Bennett

Poster Session Winner Zoe Fisher

• Proposed Neutron Diffraction Studies to Elucidate the Proton Transfer Mechanism via Hydrogen Bonded Networks in Carbonic Anhydrase and Superoxide Dismutase, S. Zoë Fisher
• What can be learned about biochemical reactions from neutron diffraction studies?, Amy Katz
• Neutron Phasing Methods Applicable to D/H SIR Derivatives, David A. Langs
• Neutron protein crystallography with LADI, Flora Meilleur
• Recent Advances in Laue Data Processing, Zhong Ren
• The Molecular Mechanism of DNA Polymerases Studied by Small-Angle X-Ray Scattering (SAXS), Kuo-Hsiang Tang
• A Neutron Biological Diffractometer in J-PARC, I. Tanaka
• The Bio-Deuteration Lab at Oak Ridge National Laboratory, Kevin Weiss

Scientific Organizing Committee

• Andrew Mesecar (University of Illinois Chicago), mesecar@uic.edu
• Dean Myles (Oak Ridge National Laboratory, mylesda@ornl.gov
• Arthur Schultz (Argonne National Laboratory), ajschultz@anl.gov
• Thiyaga P. Thiyagarajan (Argonne National Laboratory), thiyaga@anl.gov

Local Contacts

• Al Ekkebus, 865-241-5644, ekkebusae@sns.gov
• Peggy Anderson, 865-241-5907, andersonpc@ornl.gov

Sponsors

• Intense Pulsed Neutron Source
• Argonne National Laboratory
• Oak Ridge Associated Universities
• Oak Ridge National Laboratory
• Spallation Neutron Source
• University of Illinois, Chicago

Workshop Presentations (pdf format)

• Time-of-flight Neutron Diffraction as an Aid to Elucidating Enzyme Mechanisms, Jenny Glusker
• Neutrons Will Play an Increasingly Important Role in Direct Methods of Phase Determination, Herbert Hauptman
• Structural Genomics Exploring Protein Structure and Function, Andrzej Joachimiak
• Structural Opportunities, Anthony Kossiakoff
• The Spallation Neutron Source and Biology, T. E. Mason
• The effects of flash-freezing on the structure of ß-galactosidase, Brian Mathews
• Current Status of Macromolecular Neutron Crystallography, Dean Myles
• Ultra high resolution structure and preliminary neutron diffraction results on Aldose Reductase, Alberto Podjarny
• Fiber Diffraction In Biology: New Opportunities From Neutron Scattering, Gerald Stubbs
• Conceptual Design and Expected Performance of the Macromolecular Neutron Diffractometer (MaNDi) for the SNS, T. P. Thiyagarajan
• If You Build it "We" Will Come: Past Experiences and Predictions, Bi-Cheng Wang

Workshop Reports and Other Documents

• Workshop Report - Conference on the New Frontiers in Neutron Macromolecular Crystallography, July 12-13, 2005
• MaNDi proposal to the Experimental Facilities Advisory Committee (EFAC), July 2004.
• Workshop Report on Neutron Macromolecular Crystallography at the Spallation Neutron Source, October 2-3, 2003, Argonne National Laboratory.
• SNS MaNDi - Proposal and Workshop Report 2003