ACA 2009

Toronto, Ontario, Canada, July 2009, www.amercrystalassn.org

Below is a summary of the report that appeared in ACA RefleXions, Fall 2009, pp. 10-46.

The 2009 ACA meeting (Local Chair: David Rose (Waterloo) – Program Chair: Jim Britten (McMaster)) had the third largest attendance ever with over 1000 registrants and exhibitors.

Calpastatin bound to the active site of calpain 2; an inspiration for the design of calpain inhibitors. Kristin Low, ACA09 Pauling Poster Prize winner.

Plenary Lectures: Ted Baker (U. of Auckland) gave a historical lecture that began by citing Louis Pasteur who first demonstrated that external form reflects internal structure. His talk cataloged the work of pioneers in crystallography and connected molecular structure with biology, chemistry, mathematics, art and architecture. Philip Coppens (SUNY, Buffalo) discussed the supramolecular solid state as a medium for photochemical studies of molecules. Shih-Lin Chang (Warren Award – National Tsing Hua U.), discussed coherent dynamical interactions in X-ray multiple diffraction and crystal cavity resonance. Svilen Bobev (Etter Early Career Award – U. of Delaware) presented his work on novel germanide structures. Michael James (Buerger Award – U of Alberta) took his audience on a journey from his early 'exposure' to X-rays at the U. of Manitoba and his doctoral studies with Dorothy Hodgkin at Oxford through his time in Alberta winding up with his present research on proteins in Mycobacterium tuberculosis.

Transactions Symposium: Speakers concentrated on phase transitions, a rigorous arena for studying the balance of forces that stabilize particular atomic conformations, with direct applications in pharmacology and drug design where stable polymorphs are critical, and in the design of devices to monitor and control technological properties.

'Would You Publish This?': Presenters 'aired their dirty laundry' in an effort to stimulate discussion about how small molecule crystallographers handle problem crystal structures of chemical importance. Issues of disorder, solvent loss, and inherently bad data were discussed. J. Tanski (Vassar College) described a structural model considered 'bad' by IUCr standards that was still useful to chemists. F. Fronczek (Lousiana State U.) presented 'Barely Publishable' porphyrin structures that were barely solvable and nearly impossible to refine yet provided critical chemical information. Subsequent discussion topics included: (a) the effort required to generate incremental improvements in structure quality, (b) methods to ensure the experimental details are included in the publication by the chemist, and (c) when is the program Squeeze appropriate and does it bias the structural model? 'Would You Publish This II?' is scheduled for the ACA 2010 in Chicago.

Small molecule problem structures: Talks addressed the benefits of using the synchrotron sources for twinned and/or highly disordered crystals, C. Beavers (Advanced Light Source, LBNL), and exploiting pseudo-symmetry in crystal structures that have a high Z' value, V. Young (U. Minnesota).

The crystal structure of a TraM-DNA complex from the F-related plasmid pED208. (Joyce Wong, U. Alberta)

Supramolecular Chemistry: Topics included intermolecular forces, non-covalent assemblies, crystal growth, materials design, pharmaceuticals, and database studies. G. Desiraju (Indian Inst. of Science) offered an insightful look at polymorphism and structures with high Z', as well as a spirited defense of the relevance of small-molecule crystallography. Other talks included: Halogen bonding, P. Metrangolo (Politecnico de Milano); host-guest chemistry, J. Wuest (Montreal); solid-state based photochemistry, M. Kaftory (Technion) and D.-K. Bucar (Iowa), and co-crystals of pharmaceutically active ingredients, S. Forbes (Kansas State) and H. Abourahma (College of New Jersey).

Professional Directions: A panel of six crystallographers (S. Ginell, Argonne Labs; J. Kaduk, INEOS Technologies; S. Sheriff, Bristol Myers-Squibb; C. Stern, Northwestern U.; P. Swepston, Rigaku Americas; C. Wilmot, U. of Minnesota; and M. Wilson, U. of Nebraska-Lincoln) answered the question 'Is there a future for crystallography?' with a resounding 'YES!' In answer to concerns about career options in crystallography in the current tumultuous economy the panel's advice was to pursue a career that you are passionate about. They stressed that a willingness to accept change affords great opportunities. A common theme among the personal stories of the panelists was that each had a supportive mentor. This theme accentuated the importance of seeking out collaborations and building relationships. A similar session, 'Professional Odysseys', aimed at informing young scientists of career options and advancement opportunities will be held in Chicago.

Educational Outreach: Presentations included descriptions of Protein Data Bank (PDB) activities for dissemination of structural data to students, educators and the general public, C. Zardecki and S. Dutta (RCSB PDB); the internet as a forum for communication, discussion and tutorials about crystallography, S. Seaver, (Toledo - www.P212121.com); and a free online teaching set of the Cambridge Structural Database (CSD) for use in undergraduate chemistry curricula, G. Battle (CCDC). Buffalo high school students discussed the possibility of a primordial genetic code. By analyzing codon use in the ancient bacteria Anaeromyxobacter dehalogenans they concluded that 3 billion years ago, a precursor to the standard genetic code used 32 codons, all ending in G or C, to encode all amino acids. B. Rupp (Q.E.D. Life Sciences) advocated the use of real molecules to help students make the connection between crystallography, symmetry, and real life problems. L. Malaspina (U. Federal de Goiás) described her experiences attending the 2009 ACA Summer School, bringing samples, collecting data, and working on data analysis with experts in the field.

Vaccine Design: I. Wilson (Scripps), B. Baker (Notre Dame), and R. Rappuoli (Novartis) discussed the applications of vaccines to viruses, bacteria and cancer. B. Chen (Harvard), B. Schief (Washington), and P. Kwong (Vaccine Research Center, NIH) highlighted diverse ways in which structural biology can address challenging stages of HIV-1 vaccine development, from epitope identification, to immunogen design and vaccine delivery.

The 2.9 Å structure of DdrB from Deinococcus geothermalis. Seiji Sugiman-Marangos, McMaster U.

Green Biochemistry: Focus here was on the production of biomass, carbon neutral biofuels, bioremediation, and biocatalysis. Three student presentations, B. Goblirsch (U. Minnesota), P. Chan (Toronto), and P. Cedervall, described structural and mechanistic studies of enzymes involved in bioremediation.

Crystallization Methods: B. Rupp stressed that modifying an obstinate protein is a more promising path to crystallization than additional screening. Z. Derewenda (U. Virginia) described how surface engineering can be used to obtain crystals of proteins otherwise recalcitrant to crystallization. B. Price (Columbia) analyzed the relationship between protein solubility and crystallization propensity and A. Dong (Toronto) discussed how excision of flexible loops and loose ends can facilitate crystallization. N. Seeman (New York) described the synthesis, construction, and X-ray diffraction analysis of 'designer' DNA crystals and their potential use for the development of drugs that interact specifically with defined sequences of DNA.

Chromatin Remodeling: New mechanisms for controlling post-translational modifications of histone proteins were highlighted and by combining crystallographic data and in vivo experimentation, R. Trievel (Michigan) identified a novel target for drug design to combat mycosial diseases.

Carbohydrate Recognition: Talks addressed design of multivalent carbohydrate mimetics as therapeutics for cystic fibrosis, A. Imberty (CNRS); specific inhibitors to control blood glucose levels in diabetes, L. Sim (Toronto), and α-mannosidase II target for inhibition of glycosylation in cancer metastasis, D. Rose (Waterloo/Toronto).

Mavis Agbandje-McKenna, Robert McKenna, John Domsic, Balendu Avvaru, Miorel Palii, Jeanne Quirit, Katherine Sippel and Balasubramanian Venkatakrishnan at the Opening Reception.

New Technology in Industry: Topics covered fragment based drug discovery, D. Davies (deCODE Biostructures), new developments in monochromator technology, R. Durst (Bruker-AXS), absolute configuration from Bijvoet differences of only C, H and N atoms, R. Scaringe (Bristol-Myers Squibb), and the effects of UV irradiation on protein crystal stability, P. Le Magueres (Rigaku).

Nanomaterials: Block copolymers (BCP) characterized by combining transmission electron microtomography and neutron reflectivity, H. Jinnai (Kyoto Inst. Tech.); anomalous swelling of polymer thin films induced by density fluctuations in supercritical carbon dioxide, P. Gin (SUNY Stony Brook - SAS SIG 2009 Etter Student Lecturer); constructing BCP-based supramolecules by associating small molecules to the side chain of one block, T. Xu (UC Berkeley); and polyelectrolyte layer-by-layer films, E. Kharlampieva (Georgia Tech.).

Cool Structures: E. Stevens (U. of New Orleans) described combining classical spectroscopic and charge density methods, and theoretical calculations to examine the exo-anomeric effect in an α,α-trehalose dihydrate.

Energy Related Materials: Two sessions covered hydrogen storage batteries and fuel cell related materials and in-situ characterization of thermoelectric and framework materials. M. Beekman (U. South Florida) presented his Etter Student Lecturer Award talk on intermetallic clathrates using X-ray powder diffraction.

Complementary Methods for Macromolecular Crystallography: Talks included computational techniques to interpret solution X-ray and neutron scattering data, D. Svergun (EMBL-Hamburg), and small angle X-ray scattering and cryoelectron microscopy, Dina Schneidman (UCSF). M. Hunter (Arizona State) described a study of Photosystem I in which a micro-jet device sent nanocrystals, containing only several thousand unit cells, into a soft X-ray beam while power diffraction patterns were recorded, demonstrating that fewer unit cells than have previously been used in micro-beam diffraction studies can give sufficiently strong diffraction to enable structural analysis.

Drug Design: P. Williams (Astex Therapeutics) discussed Fragment-Based Screening (FBS) to rapidly produce drug candidates; P. Colman (The Walter & Eliza Hall Inst.) talked about antivirals and the problem of drug resistance, and C. Abad-Zapatero (U. Illinois, Chicago) discussed new ways of plotting and analyzing FBS data. Etter Student Lecturer Ivan Campeotto (U. Leeds) discussed the use of directed evolution to locate a mutation that increased substrate specificity and stereoselectivity of N-acetylneuraminic acid aldolase.

Superconducting Materials: Highlights included the description of the links between crystal structure and the maximum transition temperature in four families of Fe-based superconductors, D. Johrendt (Ludwig Maximilans U.), and charge doping as the critical parameter for superconductivity, S. Kimber (Helmholtz-Zentrum Berlin).

Refinement Software: Descriptions of the latest improvements to REFMAC and autoBUSTER, real space refinement and automated non-crystallographic symmetry in MAIN, and using SHAKERR, E. Pozharski (Maryland) were featured. A. Brunger (Stanford U.) described a deformable elastic network to restrain sampling to prior knowledge of an approximate or homologous structure.

Instrumentation: New sources, optics, robotics and detectors were described, including the Compact Light Source, a miniature synchrotron using inverse Compton scattering to produce X-rays; the new linac coherent light source at SLAC, the first hard X-ray free-electron laser beam whose extreme peak brilliance will permit use of nanometer-sized crystals; PILATUS 6M, the first large area pixel detector; beamlines at the Canadian Macromolecular Crystallography Facility that enable high-throughput and remote data collection; simultaneous, small and wide angle data collection on the X9 beamline at NSLS; a new robotics system to perform transfers, screening and data collection on frozen samples at the ESRF; microSAXS with microfluidics technology; and a time-resolved study at APS BioCARS that combined crystallographic and WAXS techniques. The Etter Student Lecturer J. Smith (Ottawa) described exploiting area detectors to reduce Compton scattering via energy selection and to measure beamline polarization.

Cooperative Phenomena in Magnetic Materials: D. Louca (Virginia) used neutron scattering to follow the development of magnetic superstructures in Cobaltites.

Large Small Molecules: G. Sheldrick (Göttingen) discussed dual space and charge flipping methods in the SHELX suite. Other talks concerned refinements of disordered (104 atoms) fullerene structures, M. Olmstead (UC Davis); successful phasing of a (2550 Da) molecule with one chlorine atom, P. Loll (Drexel); using neutron and X-ray diffraction data on deuterated crystals of rubredoxin to locate H atom positions, A. Gardberg (ORNL); incommensurately modulated structures with Z' >1, C. Brock (Kentucky), and determining small protein structures by powder diffraction, P. Stephens (SUNY-Stony Brook).

Tips & Tricks of the Computing Trade: Speakers discussed a detailed description of twinned crystal indexing with CELL_NOW, G. Sheldrick; new visualization tools in the ISAW package for time-of-flight Laue single-crystal neutron diffraction, C. Hoffmann (ORNL); and development of the GSAS program suite, B. Toby (APS).

Accuracy and Standards in Powder Diffraction: Talks covered standards, requirements and certification procedures, J. Cline (NIST), and quantitative analysis of clay-containing minerals, O. Omotoso (NRC). Difficulties and possible strategies for overcoming them were reported, as was gauging the reliability of a Rietveld refinement using singular value decomposition to achieve the accuracy and precision of single-crystal techniques, P. Mercier (NRC)

Ferroic & Multiferroic Materials: V. Kiryukhin (Rutgers) described diode effects in single crystals of multiferroic BiFeO₃ in which the electric current is highly non-linear, temperature dependent, unidirectional and flowing in the same direction as the electric polarization; Etter Student Lecturer J. Wen (Brookhaven) discussed the unusual finding that an external magnetic field can affect the magnitude and correlation lengths associated with the charge order in LuFe₂O₄, and C. Stock (Rutherford Appleton Labs, ISIS) described the structure of one of the most highly piezoelectric materials known. Ferroic materials include ferroelectrics, ferromagnets, and ferroelastics, whereas multiferroic materials are those in which two or more ferroic order parameters are present in a single phase; as such these materials possess enormous potential for industrial device applications.

Membranes and Associated Proteins:Topics ranged from cholesterol interactions with the lipid membrane to atomic resolution structures of membrane proteins. U. Perez-Salas (Argonne) discussed bicelle-based methods for membrane protein crystallization. M. Mueller (ETH Zürich) described the structure of the dodecameric membrane pore formed by cytolysin A and rearrangements that take place upon membrane insertion and pore formation.

Structural Enzymology: S. Liu (Pfizer) told how he took advantage of a less than stellar catalytic rate to trap intermediates and observe the reaction mechanism of a pharmaceutically important enzyme. Etter Student Lecturer A. Bah (Washington U.) combined classical enzymology and structural biology to engineer an allosteric switch into thrombin to help shut off the coagulation cascade. T. Maier (ETH Zurich) presented a movie illustrating how the substrate of the eukaryotic fatty acid synthases, a hetero-oligomeric structure, is shuttled from one reaction center to the next. IUCr President, Sine Larsen (U. Copenhagen), described substrate recognition and catalysis in polysaccharide lyases crucial to the clarification of apple juice. A. Kovalevsky (LANL) used time-of-flight neutron crystallography to determine exactly how xylose isomerase catalyzes the interconversion of glucose and fructose.

(Abstracted from ACA RefleXions, Fall 2009, pp. 10-46)

ACA Poster Prize Winners

• Pauling - C. Kimberlin (Scripps Inst.), Kristin Low (Queens U., Canada)
• IUCr Prize - C. McCrimmon (U. of Virginia)
  
• Journal of Chemical Crystallography - B. Vanchura II (Michigan State U.)
  
• Protein Data Bank - M. Korczynska (McGill U.)
  
• Oxford Cryosystems - M. Warren (U. Bath, UK)
  
• AIP Undergrad. Research - C. McCrimmon (U. of Virginia) and P. Caravalho Jr (Michigan State U.)