National Institute of
General Medical Sciences

A joint meeting of the principal investigators of the Protein Structure Initiative (PSI) research centers and the advisory committee was held at the National Institutes of Health, November 14-15, 2002.

During the first day, the principal investigators reviewed their progress to date, discussed specific problems and bottlenecks, and discussed lessons from the pilot initiative that can assist in the design of the second, or production, phase. Their presentations were open to all of the principal investigators and provided an excellent exchange of information between the principal investigators and advisory committee members. On the second day, the meeting was restricted to members of the advisory committee and NIH staff. Each member of the committee briefly summarized his or her impression of the present status of the initiative. Afterwards, a general discussion was held regarding formulation of plans for the second phase.

Also, plans were reviewed for members of the advisory committee to visit each of the PSI centers during February 2003.

Perhaps the most striking feature of the meeting was the high praise that was expressed by every member of the advisory committee for the progress that has been made. The dramatic improvements in technology that have been achieved, particularly in the areas of cloning and protein expression as well as in nano-crystallization, are very impressive. Also major improvements have been made in automatic or near-automatic X-ray structure determination. These innovations will not only benefit the PSI but also the field of structural biology as a whole. The committee identified the following areas which need monitoring.

1. Better Communication with the Outside Community

Individuals close to the PSI are uniformly impressed by the rapid progress that is being made. However, this progress may not be apparent to other structural biologists or to members of the bioscience community in general.

In order to make the results that have been obtained more visible, it was suggested that it might be possible for one of the structure-oriented journals to run a monthly feature summarizing the accomplishments of the PSI. The report might include a picture of each of the structures determined that month as well as highlights of selected structures.

Another suggestion was to explore the possibility of publishing an overall summary of progress to date in Science or Nature. The summary article could include a full-page illustration showing the variety of structures that have already come from the initiative.

Also in the context of communicating with the broader community, it was noted that arrangements are being made for NIH staff and advisory committee members to give presentations and answer questions at the upcoming annual meetings of the Biophysical Society and the Protein Society.

2. Laboratory Information Management System

Several of the principal investigators commented on the time and effort that has been required to establish their information management systems. Committee members who are knowledgeable in the area agreed that this is indeed a daunting task. They also noted that a laboratory information management system needs to be highly tailored to the individual needs of the group that it serves. For this reason, it seems preferable to allow each group to continue with the development of its own system. In the longer term, however, assurance must be provided that the wealth of information being accumulated by each PSI research consortia will be available to the scientific community at large.

3. Structure versus Function

The emphasis of the PSI has been on structure, that is to determine representative structures from all protein families. The committee strongly feels that this overall emphasis needs to be maintained. At the same time, however, there are circumstances when a new structure determination may suggest immediate functional ramifications. The committee does not recommend, as a general procedure, that designated funds be included within the PSI for functional studies. At the same time the committee was relieved to know that NIGMS is able to organize a short-turn-around supplement program for related functional studies, such as for work to be done with a collaborator who is not part of the PSI.

4. How Many Production Groups?

The advisory committee has an open mind as to how many groups should be funded in the second phase of the PSI. It seems too early to make this determination.

5. Ongoing Technology Development

As noted above, there have been dramatic improvements in technology to permit high throughput cloning, protein expression, purification, and crystallization. Improvements in crystal evaluation, screening, and data collection are also in progress. Judging by the transformations that have occurred within the past couple of years, there is every reason to expect that additional major improvements will be forthcoming. Therefore, it is important that the second phase of the PSI allow for the support of ongoing technological developments.

Summary

The advisory committee was highly impressed with progress of the PSI. Suggestions were made that would make this progress more apparent to the outside community. Planning has now been initiated for the second phase.

David Davies
Chris Dobson
Anthony Kossiakoff
Eaton Lattman
Rowena Matthews
Franklyn Prendergast
Chris Sander
Gerhard Wagner
Cathy Wu
Brian Matthews, Chair

Report Submitted December 5, 2002
Chair of the Protein Structure Initiative (PSI) Advisory Committee,
Working Group of the National Advisory General Medical Sciences Council