Crystallography of molecular biology

The June 2000 Erice Course on Crystallography of Molecular Biology consisted of two parallel meetings, sponsored by the IUCr and by the Int’l Union of Biochemistry and Molecular Biology, and financed by Nato under the ASI Program.

On Sunday, May 28 the main court of the E. Majorana Centre was dedicated to Dorothy C. Hodgkin, a former director of the Int’l School of Crystallography in Erice. The Erice Vaciago Prize for the most dynamical 'student' (under 35) in attendance was awarded to Bostjan Kobe. Canadian astronaut Julie Payette presented a special evening lecture on her ten days extraterrestrial flight.

Methods for macromolecular crystallography

Directors: L.N. Johnson and D. Turk

A. McPherson described new approaches to monitoring crystal growth by atomic force microscopy and G. DeTitta showed quantitative improvements to automate crystal growth – for high throughput structure analysis - 1536 simultaneous trials.

K. Branden gave an overview of macromolecular beam line facilities world wide (48 total, 20 in Europe and 20 in USA) and demonstrated their advantages for structural biology and the prospects for the future. Thompson described the experimental set up at synchrotron sources for multi-wavelength measurements including the parameters of the synchrotron required, the tuneable wavelength, and the basis of the method for phase determination. S. Ealick took up the theme of detector development, explaining the physical principles behind current detectors. E. Garman gave an account of the use of cryomethods (100 K), that have become so important in the field.

Data processing was admirably covered by A. Leslie with lectures and by Z. Otwinowski with hands-on computer tutorials in small groups: both practical aspects and considerations about errors that are still problematic were covered.

Phase determination was divided into ab initio and molecular replacement methods. G. Sheldrick and H. Hauptman described their application when high resolution data (1.2 Å) are available and the routine for location of anomalous scatterers at lower resolution (3 Å). J. Navaza and M. Rossmann described the powerful methods of molecular replacement. Only 9% of structures solved in 1999 contained a new fold. This also introduced non-crystallographic symmetry averaging and solvent flattening in phase determination. E.Weckert described the 3-beam method for experimental phasing.

Computer graphic displays and interpretation of electron density maps were covered by A. Jones, and R. Henderson illustrated the use of electron microscopy to determine structures from 2D arrays and the convergence of X-ray and EM methods was discussed.

Chemical Prospectives

Directors: M. Jaskolski and D.I. Stuart

The school reflected the 'state of the art' of the Crystallography of Molecular Biology bringing together experimentalists, theoreticians, biochemists, crystallographers and electron microscopists. Advances in macromolecular crystallography have led to an understanding of enzyme catalysed reactions, control of gene expression, regulation by phosphorylation and recognition in signal transduction pathways, and immune response, energy transduction, of membrane proteins and ion channels, and the assembly of viruses from component proteins. The most recent results presented by leading scientists in the field gave the audience the idea of the terrific improvements achieved in the understanding. Young participants presented their results as oral and poster presentations.

Recent results concerning membrane proteins, protein nucleic acid interactions, nucleosome structure, and the 30S subunit of the ribosome were presented.

Sessions were devoted to the combined utilization of Electron Microscopy and X-ray Crystallography, the potential of the new third generation synchrotron facilities, and the contributions of crystallography to structural genomics.

Advances in MAD and SAD phasing (W. Hendrickson & A. Brunger), high resolution structure determination (K. Wilson, York, UK), automatic structure interpretation (T. Terwilliger, Los Alamos, USA and D. Turk, Ljubljana, Slovenia), non-crystallographic averaging (R. Read, Cambridge, UK), maximum likelihood refinement (E. Dodson, York, UK) and ab initio phasing methods (G. Bricogne, Cambridge, UK) were described in detail. The school featured hands on tutorials in which small groups of participants learned first hand from the experts at the computer workstations.