Oeiras, Portugal, November 2004
The second BioCrys Course on ‘Fundamentals of modern methods in biocrystallography’, organized by M.A. Carrondo (ITQB Oeiras, Portugal) and T. Schneider (FIRC Inst. of Molecular Oncology, Milan, Italy) took place at the Inst. de Tecnologia Química e Biológica in Oeiras, Portugal from November 19-26, 2004. The course was supported by the MAXINF network (www.maxinf.org, HPRI-CT-2000-40021), the SPINE project (www.spineurope.org, QLG2-CT-2002-00988), and the IUCr. It brought together 34 students and 19 tutors from 16 different countries.
Subtitled ‘What you always wanted to know about crystallography but never dared to ask ...’, the course aimed at teaching fundamental theoretical concepts of macromolecular crystallography to scientists in the early stage of their crystallographic careers. This is particularly important due to the rapid development of the field and the fact that many young researchers do not receive a formal education in crystallography. Additionally, with the introduction of high-throughput methods, the need to understand and grasp the theory behind modern methods will be critical to tackle the difficult problems that will not be solved by automated procedures.
Lectures and tutorials covered topics from the cooling of crystals to the validation of the final structural model. Lectures were held in the morning and interactive practicals and tutorials in the afternoon. For the computational tutorials, 18 Linux-computers were set up by P. Matias and M.M. Rato (ITQB, Portugal). Tutors or invited speakers presented evening lectures about a current topic in structural biology.
E. Hough (U. Tromsø, Norway) laid out the basics of crystallography in real and reciprocal space. C. Hermes (EMBL Hamburg, Germany) gave an overview of the principles of X-ray sources and detectors and E. Garman (Oxford U., UK) lectured and demonstrated the practical side of crystal cooling and data collection. K. Cowtan (U. York, UK) guided the students through the world of structure factors and how they relate to electron densities in his web-based tutorial (www.yorvic.york.ac.uk/~cowtan/sfapplet/sfintro.html). Understanding the basics was complemented by a tour of crystallographic resources on the internet, presented by F. Enguita (ITQB Oeiras, P).
Strategic questions of data collection and the principles of data processing were addressed by Z. Dauter (Argonne Nat. Lab., USA) and A. Leslie (MRC Cambridge, UK). This included a tutorial on ‘How to read (and understand...) the International Tables’ given by Z. Dauter.
Lectures and tutorials focused next on experimental phasing. G. Leonard (ESRF Grenoble, France) gave an introduction to the use of anomalous scattering in macromolecular crystallography. The MIR-method was discussed and later demonstrated in a tutorial by C. Vonrhein (GlobalPhasing Cambridge, UK). The substructure solution process and MAD-phasing where covered by T. Schneider (IFOM Milano, Italy). K. Cowtan discussed the principles of different density modification techniques used for phase improvement, followed by Z. Dauter, who explained various aspects of SAD-phasing. Molecular Replacement was introduced and discussed with the help of examples by P. Matias. T. Schneider lectured on refinement and model precision and C. Frazão described how the particular problems encountered with twinned crystals can be tackled. Tutorials on this day were still concerned with phasing (MAD phasing by T. Schneider and density modification by K. Cowtan).
The central topics of the last two days were molecular replacement and both manual and automated model building. A. McCoy (Cambridge U., UK) introduced the basic concepts of maximum likelihood as used in crystallography and then led the students through the practical use of these in molecular replacement. Automated model building and refinement was discussed both from a methodological and practical point of view by A. Perrakis (NKI Amsterdam, NL). M. Kjeldgaard taught the principles and practicalities of manual model building. The discussion of model building was complemented by overviews of what can be achieved with atomic resolution crystallography by K. Wilson (York Univ., UK) and of how the correctness of a model can be assessed by different validation criteria by M. Archer (ITQB Oeiras, Portugal). Evening lectures included two lectures on ribosomes by A. Liljas (Lund Univ., Sweden), overviews of automation at ESRF (G. Leonard) and of SPINE (K. Wilson).
During the entire course, a box to which specific ‘burning questions’ about crystallography could be submitted anonymously was available. These questions were later answered by the tutors in a special session. This proved to be very popular and gave valuable feedback to the tutors.
All participants were staying in the same hotel, which provided an excellent interactive environment. The City Council of Oeiras generously invited all participants to a dinner in the Fabrica de Pólvora a historic landmark of the region. Another evening was spent at a typical Portuguese restaurant enjoying regional cuisine and regional folk dances.
We thank the European Union and the IUCr for the generous support that made it possible to organize this second edition of this course on the fundamentals of crystallography. We are also grateful to the informatics staff of ITQB and especially to M. Mateus for efficient handling of course administration and logistics.Maria Arménia Carrondo, Thomas R. Schneider, Organizers