Meeting report

Neutrons in Biology conference

Santa Fe, NM, USA, October 2009

The International Conference on Neutrons in Biology was held in Santa Fe in October 2009 to review recent progress and to celebrate Benno Schoenborn's many contributions to the field. Following a very distinguished career in national research laboratories and universities around the world, Benno formally retired from LANL in May 2009, however he will continue as Senior Fellow at LANL and Professor at the U. of Sydney.

Neutron protein crystallography is a powerful technique to investigate mechanisms of enzyme activity, inhibitor binding etc. where details of H positions, particularly in the vicinity of the active and/or recognition sites, lead to a better understanding of molecular interactions. Ryota Kuroki (JAEA) presented two examples of drug binding to receptors - porcine pancreatic elastase (PPE) with potent inhibitor FR13080, and human immunodeficiency virus type-1 protease (HIV-PR) with potent inhibitor KNI-272. Julian Chen (Goethe U.) is determining the structure of diisopropyl fluorophosphatase (DFPase), a calcium-dependent phosphotriesterase, in order to better understand its ability to detoxify a wide range of organophosphorous nerve agents. Investigations into the molecular mechanism(s) of sweet taste were presented by Susana Teixeira (Keele U., ILL) using the structure determination of the artificial sweetener, thaumatin. Andrey Kovalevsky (LANL) presented the findings of a very elegant study on the Bohr effect in the allosteric binding and release of oxygen in Hb. Carbonic anhydrase is a ubiquitous metalloenzyme that reversibly converts carbon dioxide to carbonic acid and bicarbonate ions in the mammalian respiratory system. Zoë Fisher (LANL) described the latest results of studies on the hydrated proton-transfer wire implicated in the enzymatic process. Jenny Glusker (Fox Chase Cancer Centre) illustrated recent work on the movement of H atoms involved in sugar conversion by d-xylose isomerase - an important enzyme for biofuel production.

Studies of the phase transitions, hydration, folding/unfolding and drug binding in DNA using complementary X-ray and neutron scattering and diffraction techniques was presented by Trevor Forsyth (Keele U., ILL). Developments in experimental techniques were highlighted and recent results presented.

Progress toward developing a unified model for protein dynamics was presented by Hans Frauenfelder (LANL). Such a model requires a good understanding of backbone motions as well as interactions with individual solvent molecules and the bulk. Fluctuations in the hydration shells and bulk solvent have a significant influence on protein structure and dynamics.

Recent developments in instrumentation for neutron protein crystallography stressed the importance of small crystal size (∼0.1-0.2 mm3), macromolecular deuteration, increased neutron flux, more and larger area detectors, and increasingly sophisticated software for data processing and analysis. The features and performance were presented for iBIX at JPARC (Ichiro Tanaka, Ibaraki U.); LADI-III at the ILL (Matthew Blakeley, ILL); TOPAZ at the SNS (Xiaoping Wang, ORNL), and PCS at LANSCE (Andrey Kovalevsky, LANL).

A highlight of the conference was a mini-symposium on 'Neutrons for Renewable Energy and the Environment'. Various aspects of this priority field of research were presented, from detailed studies of the hydrogen-bonding network in cellulose fibres (Yoshi Nishiyama, CNRS) to the complex multi-component cellulosic biomass structures including longer length scales (Paul Langan, LANL). Looking for a better understanding of enzymatic and/or chemical processing of cellulose fibres, Mike Kent (SNL) used the SANS technique to monitor enzymatic digestion in situ, and Venki Pingali (ORNL) explored the structural effects of acid pre-treatment. Molecular modelling of the hydrogen-bonding network in cellulose fibres was reported by Gananakaran (LANL).

The PHENIX (www.phenix-online.org) and nCNS (mnc.lanl.gov) software packages are being developed for the international neutron macromolecular crystallography community by an NIH-funded consortium of scientists led by Paul Langan (LANL) and Paul Adams (LBL). These packages now include a new generalized X-ray and neutron crystallographic analysis approach that provides more accurate and complete structures for biological macromolecules. Pavel Afonine (LBL) presented an excellent overview, and then together with Marat Mustyakimov (LANL) led a workshop on 'Computational Tools in Neutron Crystallography' in which informal discussions and hands-on tutorials demonstrated the many features of both packages.

Small-angle neutron scattering (SANS) is a valuable technique to investigate structure on longer length scales. William Heller (ORNL) described the dedicated Bio-SANS instrument at HFIR and Cameron Nylon (STFC) described the new SANS2d instrument at ISIS, which is an example of the next generation of SANS instruments with two tandem 2D detectors. Rex Hjelm (LANL) presented the findings of a fascinating study using SANS to unravel the complex dynamic process of moving cellular organelles along the microtubule network.

Neutron reflectivity is used extensively to study the structure of biological membranes. Jarek Majewski (LANL) used a thermo-responsive polymer to tailor the local curvature of a fully hydrated tethered bilayer, thus forming an excellent model for an intact biological membrane. Luke Clifton (U. of Reading) explored the interaction of puroindolines - seed defense proteins in wheat - with lipid bilayers to better understand wheat endosperm texture, and also provide valuable insight into protein-lipid interactions.

[Presentation to Benno Schoenborn] Dean Cole from the Office of Biological and Environment Research of the US Department of Energy presenting Benno with a letter from DOE headquarters thanking Benno for his service. The letter is being held by Alan Hurd, the Director of the Manual Lujan Neutron Science Center at Los Alamos National Laboratory.

Benno Schoenborn was the distinguished after-dinner speaker and entertained guests with the 'History of Neutrons in Biology'. This was a colourful narrative of the development of the unique contribution of neutron scattering applied to biological structures. There were numerous anecdotes. Benno first discussed the possibility of neutron diffraction to investigate H bonding in proteins with Herman Watson, Uli Arndt, John Kendrew and Christopher Nobbs in the MRC tearoom in 1965. As usual, Benno was of the view that just because something was considered to be almost impossible did not mean it could not be done. Two years later, with support from Christophe Hirs and using Walter Hamilton's single-detector diffractometer at HFBR (BNL), Benno collected the first diffraction peaks from a rather large (by today's standards) myoglobin crystal. It took almost a year to collect a complete dataset and the results were published in Nature in 1969. Benno's career is a kaleidoscope of people, places and achievements, always pushing the limit in knowledge, theory, instrumentation and software, the impact of which will be substantial well into the future. Throughout his career Benno supervised and encouraged a generation of students and Early Career Scientists, and is an inspiration and mentor to many.

The organizers are grateful for financial support from Materials Research Society, the Office of Biological and Environmental Research of the US Department of Energy, and the Los Alamos National Laboratory. The proceedings of the conference will be published in a special issue of Acta Crystallographica.

Paul Langan (Conference Chair) and Robert Knott