First International Structural Genomics Meeting
sponsored by NIGMS and the Wellcome Trust

The Wellcome Trust Genome Campus, Hinxton Hall Conference Centre
Hinxton, Cambridgeshire, UK
April 4-6, 2000

• Agreement
• Roster
• Agenda

Agreed Principles

Coordination of International Programs in Structural Genomics

I. Introduction

Success of the genome sequencing projects and major advances in methods of protein structure determination have led the structural biology community to propose the large scale mapping of protein structure space. This structural genomics initiative aims at the discovery, analysis and dissemination of three-dimensional structures of protein, RNA and other biological macromolecules representing the entire range of structural diversity found in nature. Such a complete knowledge will facilitate fundamental understanding and applications in biology, agriculture and medicine. The three-dimensional structures will be crucial for rational drug design, for advancing catalysis in chemistry and biotechnology, and for diagnosis and treatment of disease, as well as for advancing basic principles of biology.

This opportunity is made possible by rapid recent progress in several related key technologies. These include the construction of synchrotrons and high-field NMR instruments, the MAD method of phase determination, high throughput cloning and recombinant expression, a flood of information from genome sequencing projects, and new bioinformatic methods for fold assignment, model building, and prediction of function.

The following document outlines issues related to achieving this expansion of knowledge. The goal is to encourage harmonious cooperation among a broad range of public and private sector institutions in the international effort to characterize macromolecular structures in living organisms on a pan-genomic scale.

II. Goals

A.  Specific goals

1. Large scale determination and analysis of three-dimensional structures.
   
   1. To determine by experimental methods a representative set of macromolecular structures, including medically important human proteins and proteins from important pathogens and model organisms.
   2. To provide models based on sequence homology to significantly extend the coverage of structure space.
   3. To derive functional information from these structures by experimental and computational methods.
   
   
2. Development of methods for Structural Genomics.
   
   1. Methods of selecting representatives of protein families based on enhancement of structure space coverage, or functional significance.
   2. High-throughput methods for production of target proteins suitable for structure determination.
   3. Methods for high throughput data collection.
   4. Methods for automated determination, validation, and analysis of 3D structures.
   5. Methods for homology-based modeling, related methods and validation of modeled structures.
   6. Informatics systems to optimize and support the process of structure determination.
   7. Bioinformatics methods for assessing biological function based on structure and other linked biological information sources.
   8. Methods for more challenging problems of production and structure determination such as those involving membrane proteins and multimolecular complexes.

B.  Programs needed

1. Financial and organizational support for structural genomics projects.
2. Establish an international coordinating network to promote efficient application of resources and rapid dissemination of methods and results; to coordinate policies, standards, and formats; and to promote access to unique resources such as synchrotron and high field NMR facilities.
3. Support for the collection, archiving and dissemination of atomic information, experimental data, protocols, and materials.

III. Cooperation

A.  Public funding agencies can cooperate:

1. By agreeing and implementing uniform policies for deposition, quality standards, and formats.
2. By providing sustainable support for public domain programs in structural genomics.
3. By encouraging and supporting appropriate international collaborative programs.

B.  Information and Material Release in the National Structural Genomics Programs

1. The primary impetus for structural genomics is to obtain a base of freely available structural information and tools that will support advancements in wide areas of biology and medicine. Free exchange of data and materials is essential to the success of this effort, including the timely deposition of coordinates, data, and protocols.
2. For the public structural genomics programs, the following guidelines for release of structural data should be supported:
   
   1. Timely release of coordinates and associated data. Release should follow immediately upon completion of refinement. For the time being, the decision regarding 'completion' will be made by the investigator. A longer-term goal is the automatic triggering of data release using numerical criteria.
   2. Public information on progress of projects. A primary mechanism for encouraging compliance with the guideline of timely release will be openness of progress tracking for projects. Members of the programs should maintain a public web site, showing progress status on determining the structure of each target. This information will be updated frequently.
   3. Short scientific papers. Ensuring high quality of released structures is a priority. In order to help achieve this, structures released by members of the public programs may be accompanied by a short, peer-reviewed paper. These papers could be similar in format and content to the publications of small molecule crystal structures in Acta Cryst. C. The key requirement is that reviews are rapid, and the whole process of preparing the release completed in about three weeks. Normal full-length publication is of course also possible, but should not delay the release of data.
3. To promote communication and prevent unintended duplication of effort, it is desirable to openly share information on targeting of proteins for structure determination.
4. At the time of coordinate deposition and data deposition, protocols for cloning, expression, crystallization and structure determination should also be deposited, enabling re-determination of all structures in the database from time to time.
5. Material deposition of clones, cell lines, and protein samples is also encouraged, provided that satisfactory procedures can be put in place for collection, storage, and dissemination.

C.  Relationship to industrial activities

1. The structural genomics community should explore formation of an international consortium involving industrial partners to further the goals of structural genomics.
2. International efforts should be made to facilitate the eventual deposition of structures determined in the private sector, and to promote harmonious cooperation and exchange between the public and private sectors.

IV. Intellectual property rights

Raw fundamental data on the shape of natural protein molecules, including 3D positional coordinates, should be made freely available to researchers everywhere. However, intellectual property protection for inventions based on these can play an important role in stimulating the development of important new health care projects. Policies should be established to permit an appropriate balance between these goals.

V. Future Meetings

Annual meetings of representatives of the structural genomics community are anticipated for the continued discussion of these issues. The Second International Structural Genomics Meeting is being planned for April 4-6, 2001, in Virginia, USA.

These principles were supported by the participants in the First International Structural Genomics Meeting in Cambridge, UK, April 4-6, 2000.

Roster

Dr Sherin Abdel-Meguid
Suntory Pharmaceutical Research Laboratories
USA

Dr Geoff Barton
EMBL-EBI
UK

Professor Helen Berman
Protein Data Bank
Rutgers University
USA

Professor Ivano Bertini
Magnetic Resonance Center
University of Florence
Italy

Professor Sir Tom Blundell
University of Cambridge
UK

Professor Stephen K Burley
The Rockefeller University
USA

Dr Christian Cambillau
AFMB-CNRS
France

Mr. David Carr
The Wellcome Trust
UK

Dr Marvin Cassman
NIGMS NIH
USA

Dr Cyrus Chothia
MRC Laboratory of Molecular Biology
University of Cambridge
UK

Miss Nicky Clarkson
Hinxton Hall Conference Centre
UK

Dr Robert Cooke
GlaxoWellcome Research & Development
UK

Ms Anna Curson
The Wellcome Trust
UK

Professor Christopher Dobson
University of Oxford
UK

Professor Guy Dodson
University of York
UK

Dr Richard Durbin
Informatics Division
The Sanger Centre
UK

Dr Charles Edmonds
NIGMS/NIH
USA

Professor Aled Edwards
University of Toronto
Canada

Professor Roger Fourme
LURE Universite Paris-Sud
France

Professor Paul Freemont
Imperial College of Science, Technology and Medicine
UK

Professor Paul Gilna
National Science Foundation
USA

Professor Udo Heinemann
Max-Delbr¸ck-Centrum f¸r Molekulare Medicin
Germany

Professor Wayne Hendrickson
Columbia University
USA

Dr Nobuo Kamiya
RIKEN Harima Institute/Spring 8
Japan

Professor Robert Kaptein
University of Utrecht
The Netherlands

Professor Sung-Hou Kim
University of California
Berkeley
USA

Dr Richard Kramer
Novartis Pharmaceuticals Corp
USA

Dr Victor Lamzin
EMBL
Germany

Professor Michael Levitt
Stanford Medical School
USA

Professor Peter Lindley
European Synchrotron Radiation Facility
France

Dr Michal Linial
The Hebrew University
Israel

Dr Albrecht Messerschmidt
Max-Planck-Institute for Biochemistry
Germany

Dr Stefan Michalowski
OECD
France

Dr Colin Miles
BBSRC
Swindon

Dr Gaetano Montelione
CABM - Rutgers University
USA

Dr Michael Morgan
The Wellcome Trust
UK

Professor John Moult
CARB
University of Maryland
USA

Dr John Norvell
NIGMS/NIH
USA

Dr Mark Palmer
Medical Research Council
UK

Dr Ari Patrinos
US Department of Energy
USA

Professor Simon Phillips
University of Leeds
UK

Dr Debbie Poole
The Wellcome Trust Genome Campus
UK

Professor Randy Read
Wellcome Trust/MRC Building
UK

Professor David Rice
University of Sheffield
UK

Dr Ajay Royyuru
IBM T J Watson Research Center
USA

Professor Chris Sander
Millennium Predictive Medicine
USA

Mr. David Seemungal
The Wellcome Trust
UK

Dr Barbara Skene
Wellcome Trust
UK

Dr Sharon Spencer
Catalyst Biomedica Ltd.
UK

Professor Joel Sussman
Weizmann Institute of Science
Israel

Dr William Taylor
National Institute for Medical Research
UK

Dr Tom Terwilliger
Los Alamos National Laboratory
USA

Dr Jean-Claude Thierry
CNRS
France

Professor Janet Thornton
University College London

Dr Tony Wilkinson
AstraZeneca
Cheshire

Dr Shigeyuki Yokoyama
RIKEN Genomic Sciences Centre
Japan

Agenda