Macromolecular crystallography

The focus of this issue of the IUCr Newsletter is upon Macromolecular Crystallography. In the Cover Story based upon Louise Johnson's plenary lecture at the XVI Congress and General Assembly in Beijing, Louise identifies a number of cases in which X-ray crystallographic studies are contributing directly to rational drug design.

It can truly be said that there is an explosion of macromolecular structure determinations. Full color  illustrations of macromolecular structures having immediate relevance to our daily lives appear on the covers of major journals weekly. New journals are being spawned at a furious rate just to keep up with the flow.

Acta Crystallographica inaugurated a new section (D) devoted to macromolecular crystallography (Jenny Glusker, Editor). Structure, a journal edited by crystallographers Wayne Hendrickson and Carl-Ivar Brändén, also began in 1993 (published by Current Biology Limited) and includes X-ray and NMR studies of macromolecules. Nature Structure Biology was spun off from Nature to handle the large number of papers on the topic, many (and the best) of which were crystallographic reports. Some older journals are also expanding their coverage and modifying their policies to meet the onslaught. With its January 1994 issue, the Journal of Crystallographic and Spectroscopic Research changed its name to the Journal of Chemical Crystallography (J. L. Atwood, Editor) and carried papers about ribonuclease A, angiogenin, DNA drug complexes, and error estimates in protein structures. Color graphics is used with increased frequency in most of these publications with good effect. One of the first archival journals to make routine use of color, the twelve year old Journal of Molecular Graphics (W. C. Richards and V. Cody, Editors, Butterworth-Heineman) is rich with examples of the use of color to illustrate all manner of crystallographic  investigations (drugs, proteins, surfaces, salts,superconductors, etc.).

Most members of the scientific community complain about information overload and question the need for new journals. In a recent opinion piece in The Scientist, a newspaper edited by Eugene Garfield (April l8, 1994, p. 12), William Whelan contends that commercial journals proliferate in part because professional societies fail to meet the ever changing need of their members. Garfield comments that "all dynamic research fields will eventually twig, just as biochemistry and genetics developed into molecular biology, that comes inevitably with the growth of established disciplines."

Whelan contends that "scientific journal publications should be in the hands of scientific organizations thereby ensuring built-in continuity, quality control, independence, and the highest standards of reporting. This is not to say that these attributes are lacking in the  entrepreneurial efforts of private publishers, but there can be no guarantee." It is encouraging to note that with the appearance of Acta Crystallographica D and the soon to be launched Journal of Synchrotron Radiation, the International Union of Crystallography will be doing its best to meet the needs of the community it has served so well for years as the primary archival journal in the field of crystallography.

Each of these journals has unique features of special interest. Acta Cryst. D offers the most complete and detailed structure reports and a page of the latest depositions in the Brookhaven Protein Data Bank. In its paper alert each month Structure publishes thumbnail sketches of critically important papers published in the month before press date, including most new macromolecular crystallographic structure reports.

Each issue of Protein Science, a publication of The Protein Society, supported in part by the American Society for Biochemistry and Molecular Biology, comes with a diskette containing highlights of the volume. The diskette for the May 1994 issue contained illustrations of half a dozen macromolecule structures in that issue. Jane and David Richardson have been involved in the development of the software related to the production and use of the diskettes.

The most recent arrival from publishers, Current Biology Limited, is an introductory issue of Chemistry and Biology (Stuart Schreiber and K. C. Nicolaou, Editors), an interface where macromolecular and small molecule crystallography can meet and mix it up with chemists, molecular modelers, biologists, and NMR spectroscopists.

Another fine journal, in its eighth year of publication, Protein, Structure and Genetics (Wiley-Liss) adorns its covers with full color images usually taken from a crystal structure within. A future directions piece entitled "Protein Crystallographers for All" by Editor Ed Lattman (Protein Structure, Function and Genetics, pp. 103-106) should be required reading for all crystallographers. Lattman began the article as follows:

"A host of theoretical and practical improvements in crystallography continues to push back the frontiers of the field, so that ever more difficult structures can and will be solved. In coming years these improvements will also allow us to maintain or perhaps accelerate the roughly exponential growth in the number of three-dimensional structures determined. In a few years many non-crystallographic laboratories will be carrying out their own structure determinations, especially when these involve variants of a known structure, such as mutants or ligand states. Fully trained crystallographers will act as consultants, and will normally deal with only the most challenging problems in their own laboratories." Lattman goes on to offer his appraisal of the state of the art covering crystallization, detectors, sources, time resolved crystallography, very large structures, phasing, map fitting, refinement, and software.

Also required reading for macromolecular crystallographers is an editorial by Joel Janin and Jean-Renaud Garel entitled "Welfare in Academia: A View From Europe" that appeared in Protein Science, 1994, (539-554). The authors bravely address questions concerning tenure and the explotation of young scientists. They comment:

"We witness this pauperization of science as bearing heavily on the next generation. Poorly paid graduate students and post-doctoral scientists on short-term contracts now form a large fraction of the staff in universities and research laboratories. Though most of their salary still comes from the taxpayer, they at least are not perceived as part of a sheltered academic world. As the system for recruiting permanent staff in scientific institutions now stands, the prospects are grim for young people. To give them a fair chance, we must change the system and offer alternatives to full tenure, which, in foreseeable budgets, can be granted to a small minority only. Once the administrative yoke of tenure is lifted, other possibilities ought to be explored, such as joint appointments in universities and industry. Limited-term positions (five years) with decent salaries would give young scientists the opportunity of proving themselves before applying for tenured academic jobs under more favorable conditions than offered by present short-term contracts, and would encourage them to look outside for positions in industry where their acquired competence can find fruitful use. Thus, a PhD course must provide training for a much wider area of activity than just Academia and its immediate surrounding."

It is my opinion that all of the journals mentioned in this column deserve to, and will, prosper because the application of techniques of crystallography continue to provide the most vital and reliable information about the structure of matter.

The space fillers scattered throughout each issue of the Newsletter are called "clip art" by the cognoscenti. In keeping with the macromolecular theme, the clip art in this issue is taken from an excellent paper by Christine Orengo and Janet Thornton entitled "Alpha Plus Beta Folds Revisited: Some Favored Motifs" (Structure, 1993, 1, No.2, 105-120). Their richly illustrated paper describes a scheme for cataloging proteins having α-β folds. The letters beneath each illustration are the Brookhaven PDB code for the protein structure.

This issue marks the first effort to focus on an area of crystallography. I would like to have special issues in the future on the topics of instrumentation, materials research, mineralogy, databases, publications, education, diffraction physics, crystal growth, history, chemical crystallography, and industrial applications. Most of theses areas are represented in the IUCr by Commissions and I will be asking the Chairpersons of Commissions to assist me in planning and executing special issues. I welcome suggestions from all readers as to whom I might invite to prepare cover stories on these and other topics.  Offers from individuals willing to be guest editors of special issues will receive a warm reception.