International Union of Crystallography

BioCrys2012: Fundamentals of modern methods in biocrystallography

Summary Report


The sixth BioCrys Course on 'Fundamentals of modern methods in biocrystallography, organised by Maria Arménia Carrondo (ITQB Oeiras, Portugal) and Thomas Schneider (EMBL Hamburg, Germany) took place at the Instituto de Tecnologia Química e Biológica in Oeiras (Portugal) from 20-27 October 2012. The course was supported by FEBS, IUCr, Biostruct-X and IUBMB. It brought together 38 students from 19 different countries and 20 tutors from 9 different countries.

Subtitled 'What you always wanted to know about crystallography but never dared to ask', the course aimed at teaching the fundamental concepts of macromolecular crystallography to scientists in the early stage of their crystallographic career. This is particularly important as the field is developing very rapidly and because many young researchers do not receive a formal education in Crystallography. In fact, while learning the efficient use of automated tools in crystallography, it is also critical to understand the underlying concepts for tackling difficult problems of structural biology that are not amenable to the current generation of these tools.

Lectures and tutorials covered topics all the way from the cooling of crystals to the validation of the final structural model. A typical day began at 9:00h with a 15 min. recapitulation of the concepts discussed during the previous day given by Thomas Schneider. Lectures ran from 9:15h to 13:00h and interactive practicals and tutorials from 14:00h to 17:30h. For the computational tutorials, a cluster of 18 Linux-computers was used, especially set up for the course by Pedro Matias (ITQB, P) who also introduced the participants to the computing network. In the first two days a poster session was included in the program where all the students presented and discussed their own projects.

During the first days, Ed Hough (Univ. Tromsø, N) laid out the basics of crystallography in real and reciprocal space. Christoph Hermes (EMBL Hamburg, DE) gave an overview about the principles of X-ray sources and X-ray detectors and Elspeth Garman (Oxford Univ., U.K.) lectured and demonstrated about the practical side of crystal cooling and data collection. Andrew Leslie (MRC Cambridge, U.K.) addressed data processing and integration. Kevin Cowtan (York Univ., U.K.) guided the students through the world of structure factors and how they relate to electron densities in his web-based tutorial, while management and dissemination of structural data were revised by Isabel Bento (ITQB, P). Sample preparation and characterization was presented by Rob Meijers (EMBL Hamburg, DE) while strategic questions of data collection and both theoretical and practical aspects of data processing were addressed by Zbigniew Dauter (Argonne Nat. Lab., U.S.A.) and Andrew Leslie. This included tutorials on integration and scaling of diffraction data.

Later in the course, lectures and tutorials focused on experimental phasing. The substructure solution process and MAD-phasing where covered by Thomas Schneider. Kevin Cowtan discussed the principles of the different density modification techniques used for phase improvement and the use of maximum likelihood in crystallography. Gordon Leonard (ESRF Grenoble, F) gave an introduction to the Physics behind anomalous scattering in macromolecular crystallography and Zbigniew Dauter explained various aspects of SAD-phasing.

Molecular Replacement was later introduced by Gabor Bunkoczi (Cambridge University, U.K.). Automated model building and refinement was discussed both from a methodological and practical point of view by Anastassis Perrakis (NKI Amsterdam, NL). Various aspects of symmetry were rehearsed in a two hour tutorial on 'How to read and understand the International Tables' given by Zbigniew Dauter. Thomas Schneider lectured on refinement and the importance of taking into account model precision in the interpretation of structural data.

Bernhard Lohkamp (MBB, Stockholm, Sweden) taught the principles and practicalities of manual model building and Gabor Bunkoczi demonstrated the use of PHASER for molecular replacement.

Clemens Vonrhein cancelled his participation due to sudden health problems, and the tutorial on MIR solution with SHARP was prepared in the last minute by Pedro Matias.

Carlos Frazão (ITQB Oeiras, P) described how the particular problems that one encounters with twinned crystals can be tackled. Margarida Archer (ITQB, Oeiras, P) addressed the issue of model validation. The course closed with a tutorial on model refinement and completion run by Pedro Matias and Célia Romão (ITQB, Oeiras, P).

Evening lectures tackled very important and especially relevant topics. Poul Nissen (University of Aarhus, DE) gave the IUBMB lecture on Crystallographic studies of membrane proteins - challenges and advantages, and Adrian Mancuso (European XFEL, Germany) addressed a very exciting topic on the future use of X-ray free electron lasers in Structural Biology.

During the entire course, a box was available to which specific 'burning questions' about crystallography could be submitted anonymously. These questions were later answered by the tutors in two dedicated sessions. This system proved to be very popular and gave valuable feedback to the tutors.

Although the program was extensive, there was plenty of opportunity for all participants to interact outside the formal program of the course. In particular, the fact that all participants were staying in the same hotel close to Oeiras, Hotel Praia-Mar, provided a good environment to mix and to talk to each other, not necessarily always about crystallographic subjects.

We thank our sponsors for the support that made possible to organize the sixth edition of this course on the fundamentals of crystallography. All speakers/tutors are thanked for their dedication and their continuous commitment to this course. We are grateful to the design and informatics staff of ITQB. Special thanks go to Mafalda Mateus for handling administration and logistics of the course very efficiently.

Maria Arménia Carrondo, Thomas R. Schneider, Organizers of BioCrys2012