To provide a thorough introduction to the refinement and validation of protein structures determined by X-ray crystallography. The course will take participants from the theoretical foundation of the procedures in current use to a practical stage where they master the disciplines and the appropriate software. The course will provide participants with sufficient skills to carry out and evaluate the refinement and validation of standard case protein structures at different resolutions suitable for acceptance by peer-reviewed international journals.

X-ray crystallography is the most powerful experimental method for determining three-dimensional structures of proteins. Thanks to progress in gene technology, methods for X-ray data collection and computer technology, several thousand different protein structures are known today. Automated procedures for structure determination and refinement are gaining increasing use by e.g. students, researchers associated with structural genomics centres worldwide and industry. However, since these methods have pitfalls, researchers outside the field of structure determination should appreciate methodical limitations in order to understand protein structure validation. Clearly, people working within the field must be sufficiently familiar with both the theory and practice of crystallographic refinement and validation in order to avoid releasing questionable structures to the wide range of research communities that use and depend on reported structural data.

Lectures will cover:

• Introduction to R-values and different target functions in crystallographic refinement
• Graphic model building/adjustment in structure refinement
• The PHENIX software environment
• Integrated automated model building and refinement in ArpWarp
• Structure refinement of low resolution, DEN-assisted refinement
• Structure refinement at high/ultra high resolution
• Protein structure validation 

Practical exercises will cover:

• Refinement of protein structures down to 3.5 Ångstrøm resolution
• Refinement of molecular replacement structures and protein-ligand complexes at medium resolution 
• Refinement of high/ultra high resolution protein structures
• Protein structure validation

The  one-week course will comprise about 16 lectures, 16 hours of practical exercise, and four workshops.

Group presentations and individual presentations can be anticipated during the practical exercises.

Course directors will assess individual performance and  active participation on a pass/fail basis.

9 to 13 January 2012.

3 ECTS credit points (European Credit Transfer System).

76 working hours (30 for preparation, 36 for course, and 10 for group and individual presentations).

Associate Professor Ole Kristensen, Professor Jette Sandholm Kastrup, and Associate Professor Karla Frydenvang, Department of Medicinal Chemistry at the Faculty of Pharmaceutical Sciences, University of Copenhagen.

Total course fee: DKK 8,100 (including lunch),

of which operating costs: DKK 1,900.

10 November 2011.

16 participants.

The course is part of a joint initiative (Aarhus University, Faculty of Pharmaceutical Sciences at the University of Copenhagen, and Faculty of Science at the University of Copenhagen) to provide a solid background to PhD students in central aspects/disciplines of protein crystallography with three course modules: "From Protein to Data" (module 1), "Getting Phases" (module 2), and "Refinement and Validation" (module 3). Students are recommended to take modules 1 and 2 or acquire similar experience as background for module 3. Module 1 is offered at the Faculty of Science at the University of Copenhagen, module 2 at Aarhus University and module 3 at the Faculty of Pharmaceutical Sciences at the University of Copenhagen.

Applicants enrolled in the part-time MIND master's programme may take the course.

The course will be held in English.