Fundamentals of modern methods in biocrystallography

[Oeiras group] Participants at the course on Fundamentals of Modern Methods in Biocrystallography, Oeiras, Portugal.

The first BioCrys-Course on Fundamentals of Modern Methods in Biocrystallography, organized by M. Arménia Carrondo (ITQB Oeiras, Portugal) and T. Schneider (U. of Göttingen, Germany) took place at the Inst. de Tecnologia Química e Biológica in Oeiras, Portugal in October, 2002 with support from the European Union, MAXINF network ( and Astra Zeneca. It brought together 30 students and 20 tutors from 18 different countries.

The course presented fundamental theoretical concepts of macromolecular crystallography to scientists in early stages of their crystallographic careers. This is particularly important due to the rapid development of the field and also due to 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 certainly be critical to tackle the difficult problems that will not be solved by the 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. A cluster of 16 Linux-computers were set up for the course by P. Matias, F. Enguita and D. Aragão (all from ITQB, Portugal). Tutors or invited speakers reported about a current topic in structural biology in an evening lecture.

J. Drenth (U. Groningen, The Netherlands) laid out the basics of crystallography in real and reciprocal space. C. Hermes (EMBL Hamburg, D) gave an overview of the principles of x-ray sources and detectors and E. Garman (Oxford U., UK) lectured and demonstrated about the practical side of crystal cooling and data collection. A tour of crystallographic resources on the web collected was presented by F. Enguita (ITQB Oeiras, Portugal).

Strategic questions of data collection and the principles of data processing were subsequently addressed by Z. Dauter (Brookhaven Nat’l Lab, USA) and A. Leslie (MRC Cambridge, UK). This included a 2 hour tutorial on 'How to read (and understand ...) the Int'l Tables' given by Z. Dauter and an overview about the various statistical descriptors in use for crystallographic data by C. Frazão (ITQB Oeiras, Portugal).

The MIR-method was first discussed and later practised in a tutorial by C. Vonrhein (GlobalPhasing Cambridge, UK). The substructure solution process and MAD-phasing where covered by T. Schneider (U. Göttingen, Denmark); the theoretical basis and recent successful applications of SAD-phasing were described by Z. Dauter. Rag de Graaf (U. Leidern, The Netherlands) reported about new matrix-based methods for solving substructures in an evening lecture. K. Cowtan (U. York, U.K.) discussed the principles of the different density modification techniques used for phase improvement and guided the students through the world of structure factors in his web-based tutorial ( R. Read (U. Cambridge, UK) described the phasing process in the framework of structure factor probabilities and maximum likelihood.

Lectures and practicals on molecular replacement and the self rotation function were given by R. Read, P. Matias, and M. Archer (ITQB Oeiras, P), and P. Lindley (ITQB Oeiras, Portugal) gave an overview of the past, present, and future of synchrotron radiation sources.

After taking the students from crystals to an interpretable electron density map in six very dense days, the first part of the course finished with a dinner in the Fabrica de Pólvora, to which the City Council of Oeiras had generously invited all course participants. The following day was the very much earned free day, which most participants enjoyed during a visit to Lisboa.

The course continued with instruction on methodologies used in the determination of ribosomal structures (D. Brodersen, MRC Cambridge, UK), the use of the Cambridge Structural Database (F. Allen and G. Battle, CSD Cambridge, UK), crystallographic model-building was practiced in a tutorial run (F. Enguita), structure refinement (P. Gross, U. Univ, The Netherlands), the ideas behind automatization of crystallographic model-building (A. Perrakis, NKI Amsterdam, The Netherlands), dealing with twinned crystals (C. Frazão). Tutorials run by P. Matias and A. Perrakis revealed how both classical and automated methods were used in practice.

The course ended with lectures and tutorials on how the quality of models resulting from crystal structure determinations can be critically assessed. T. Schneider introduced different measures of coordinate precision. G. Kleywegt (U. Uppsala, SE) discussed the various indicators that can be used to judge the correctness of a structure and illustrated these by alarming examples from the literature.

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 system proved to be very popular and gave valuable feedback to the tutors.

We thank the European Union and our industrial sponsors for the generous support, the staff of ITQB, and M. João Santos and H. Cordeiro for very efficient administration.

Maria Arménia Carrondo and T.R. Schneider