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Report from the CCP4/EU 1998 Advanced Methods Refinement Workshop

Eleanor Dodson

Venue: University of York, UK

Dates: Sunday December 12th - Friday December 17th, 1998

Organisers: Eleanor Dodson and Keith Wilson.


The 3D analysis of macromolecules is now an established tool for molecular biologists. The facilities for collecting excellent data from protein crystals are improving rapidly, and in response, new refinement methods are being developed. There are more laboratories exploiting Xray techniques, and many more structures being solved, often by beginners in the discipline. It is important that knowledge of the new techniques is disseminated through the community quickly and accurately. Small hands-on training workshops where the program developers both lecture on the general principles, and supervise students working with their own data are educational for both sides.

To address this need a meeting was planned with funds coming jointly from CCP4 and from an EU Advanced Methods network (CT94-0690) (which covered Italy, Spain, Portugal, France, Germany, Benelux, and the UK). Seven UK students funded by CCP4 and 18 European students and helpers funded by the EU were accepted. There were well over 50 applicants, some from outside the EU. In future we will consider providing one CCP4 funded grant to give an Indian or Eastern European student a place.

Lecturers describing programs were: Paul Adams (CNS), Dale Tronrud (TNT), Isabel Uson (SHELXL), Garib Murshudov (REFMAC), Anastassis Perrakis and Victor Lamzin (Arp_Warp).

In addition we tried to provide a complete background to the method; the lecture program is available on the web at

Details of the course

David Watkin again introduced the fundamental mathematics and principles used to fit a model to the experimental X-ray data.

Johan Turkenburg described the nature of the experimental data, how to optimise it, and a few nightmare scenarios on ways to abuse it also.

The next two days were heavily biased towards practical requirements of getting programs running. Dale Tronrud gave an overview of macro-molecular refinement and discussed how to use TNT. Garib Murshudov introduced the use of REFMAC, Paul Adams introduced CNS, and Isabel Uson SHELXL.

Setting up the tutorials was greatly simplified by the availability of the CCP4 interface. Liz Potterton explained how it could be used to transfer data from one format to another, and the students took to it very easily. The Derwent College classroom is now equipped with 20 working SGI O2s and after some helpful tweaking by the York University Computing Service staff, these provided a superb resource.

By the Tuesday evening everyone had calculations running on their own problems.

In addition more general lectures emphasising essential skills for those carrying out refinement were given. Kevin Cowtan gave an excellent and well-illustrated lecture on maps, map bias, and their expected features. Tom Oldfield went over the geometric and conformational properties of proteins, and showed how these can be used as aids for validation. These are especially valuable when used during map interpretation.

The main topic for Wednesday was the use of Arp_Warp. Arp is useful for finding solvent molecules, or unmodelled parts of the chain. Tasos Perrakis is developing automated chain tracing algorithms which work well with structures where the data extends well past 2A. The scripts provided attempt to automate the whole procedure of rebuilding after refinement, and can be used in conjunction with REFMAC or CNS.

The final session for the students addressed questions of validation against Rfactors (Ian Tickle) and the importance of deposition and of data-bases. Fortunately the departmental seminar on the Friday was given by Geoff Barton and Kim Henrick from the EBI, and they helped broaden the perspectives of the students.

In addition these workshops give an excellent opportunity for the lecturers to describe their current research interests and to gain valuable insights from each other. Isabel Uson described the progress towards ab initio phasing; Dale Tronrud his ideas on joint refinement of related structures, Randy Read the important contribution of experimental phasing to the process of refinement, Garib Murshudov the progress towards parameterising thermal motion within crystals, Paul Adams future developments to CNS, and Kevin Cowtan the results from calculating eigen values and vectors for individual parameters of a least-squares refinement.

On the Thursday the students requested a Q&A session, where they put the lecturers in the dock. This was well organised by Fabricia Fusetti, and gave a chance for various issues to be raised. One of the most persistent is that of designing restraints for ligands. The programmers present were all very conscious of the need for simple procedures to be available.

The York Christmas party was combined with the end-of-course disco and some warm close-bonded interactions were observed.

Problems of the course

It is always difficult to select the participants, and doubtless some terrible injustices were done. There is a huge demand for in-depth teaching, but it does effectively take out at least a week of the lecturer's lives, and can only be done at occasional intervals. Being somewhat disorganised Eleanor failed to hand out a questionnaire so she has no real idea what the student complaints were! However they seemed happy, and not to be-grudge working so close to Christmas.


The lecturers were wonderful, and we owe them all a great debt of gratitude. The York Computing Service staff were extremely supportive and again helped enormously to keep the show on the road. The students all worked extremely hard, and squeezed as much as they could from the time available. We are grateful to CCP4 and the EU for funding.

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