Structural Biology Center Creates Hub for Post-Genomic Protein Research

Construction of the Structural Biology Center (SBC) on KU's West Campus began in November 2003 and should be complete in 2004, according to Dave Vander Velde, head of the Molecular Structures Group and director of the Nuclear Magnetic Resonance (NMR) Laboratory. Not only will the building house the NMR and Mass Spectrometry Labs, it will also contain the new Analytical Proteomics Lab and the Protein Structure Lab. Both of these labs are being funded by bonds provided by the Kansas legislature and NIH-funded COBRE program on Protein Structure and Function. Within the last month, two major instruments have arrived on campus: the Rigaku/MSC X-ray diffractometer for protein crystallography, and the MALDI/TOF/TOF mass spectrometer for proteomics. Development of plans for facilities for macromolecular analysis and structure will continue to unfold next year with the arrival of the 800-MHz NMR spectrometer and three cold probes (at 800, 600, and 500 MHz). The electronic components of cold probes operate at about 20 degrees above absolute zero, decreasing measurement times by at least a factor of four, while the sample is maintained at room temperature.

The building will also house the Fourier transform mass spectrometer, which has extremely high sensitivity and unmatched mass accuracy. In addition to MS, NMR, and macromolecular X-ray crystallography, the SBC will also house a satellite Molecular Graphics and Modeling laboratory, and the Biochemical Research Service Lab facilities for protein expression and purification.

Early plans for the SBC were surprisingly modest. In fact, the original impetus for its construction was to find a suitable site for the 800MHz NMR, whose large size could not be accommodated in any existing building with the possible exception of Allen Fieldhouse! What has grown out of the original plan, however, is an integrated facility for postgenomics protein research. Analytical proteomics can be used to identify new target proteins, which can be overexpressed and purified onsite, and then structurally characterized by X-ray or NMR.

Also, the Molecular Structures Group has started a major new initiative with small molecules, with the announcement that NIH has funded a center of excellence in Chemical Methodology and Library Development (CMLD) at KU. Together, the NMR, MS, and MSG labs comprise the Library Design and Analysis core of the CMLD. To meet these challenges, the MSG will be adding more than half a million dollars in new instruments devoted to analyzing samples in microtiter plates, the common currency of high-throughput screening and parallel synthesis.

The construction proposal that KU submitted to the NIH in February reflects an even higher level of integration. This $6 million project would add a two-story, 20,000-square-foot addition to the SBC, called the Molecular Library Center. The overall goal is to unite KU's cutting edge facilities for both rational, structure-based drug discovery (represented by X-ray and NMR) and diversity-based methods of drug discovery (represented by combi-chem). Only a handful of universities have this full range of capabilities. Those that do have them are in scattered locations and without scientific or administrative coordination. The combined SBC and Molecular Library Center would be a one-of-a-kind facility in academia and one that would rival the discovery resources of a sizable pharmaceutical company. •