National Institute of
General Medical Sciences

November 2006

The role of this committee is to facilitate and develop interactions between the PSI and the larger scientific community, so as to make the results available for use and wide-spread exploitation, and to allow input from the community on development and selection of targets.
 
Initial activities fall into three categories, as out-lined below.

I. Improved technology transfer from the PSI to the scientific community.

Development of new technology is a principal outcome of PSI activities. Further steps will be taken to ensure communication and utilization of the results by the broader scientific community. Initial foci are:

• Establish mechanisms to make commonly used protein production protocols more available.
  The PSI and other structural genomics centers now have extensive experience of the production of pure material for thousands of proteins. A central archive of the most common standard protocols will be created, in a form that will provide a useful resource for others.
• Release of data on benchmarking and testing of protein production methods.
  In addition to the development of standard protocols, PSI centers have experimented with a wide range of alternatives, such as refolding kits, various fusion proteins, cell free systems, mutagenesis, reductive methylation, and a number of Eukaryotic expression systems. These results will be made available in a manner that will allow other biologists to make maximally informed decisions when choosing an expression system for a particular difficult expression problem.
• Establish mechanisms to make instrumentation more available.
  The PSI centers have also developed extensive instrumentation for many aspects of structure determination, especially robotics. Mechanisms will be developed for making this technology more available.
• Production of reviews on developed technology.
  Journal articles and journal special issues will be produced.

II. Improved distribution and exploitation of experimental and model structures produced by the PSI

The large number of PSI structures and associated models require new mechanisms of distribution and access, so that the results can be maximally utilized. Three initial steps are proposed, two relatively straightforward, one longer term.

• Representation of the coverage of structure space.
  A web resource will be developed, providing details of coverage of protein space and specific genomes by experimental structures and structure models of different quality.
• Mechanisms for exploiting PSI structures for functional studies.
  The set of PSI structures and associated models constitutes a very substantial resource for studies of protein function, and new mechanisms for its utilization are needed. As one step in this direction, the Center for Eukaryotic Structural Genomics is developing software and a database for identifying those members of the scientific community most likely to be interested in a particular protein structure.
• Develop a general protein structure resource – an efficient means of conveying the best possible and most relevant structural information, experimental and based on models, to non-structure oriented biologists.
  A recent workshop led by Helen Berman has produced a white paper (Berman et al., Structure. 2006 14:1211-7) outlining some of the infrastructure needed in this area.

III. Develop Community interactions with particular biology groups.

• A. Solicitation of targets from the structural community.
  PSI policy calls for a proportion of targets to be solicited from the broader scientific community. To this end, a central web site is under development, where requests for structures that would be particularly desirable can be entered.
• Interaction with genome sequence centers.
  There are many common interests between the genome sequence centers and the PSI. One half-day meeting has already been held to begin to explore these. The longer term goal is to develop mechanisms for identification of targets and for materials exchange between the two communities.
• Generation of target sets in conjunction with specific biological groups.
  The PSI target strategy includes finer grain coverage of selected families on the basis of biological, medical or functional interest. Where-ever possible, these target sets will be developed in consultation with appropriate biologists.

Steering Subcommittee on Scientific Community Interactions
Chair:  John Moult
Members: Aled Edwards, Janet Thornton
Consultant: David Eisenberg