Structural Biology
and Proteomics

Overview
People
Courses
Facilities

The Structural Biology Research Corridor

The Structural Biology Research Corridor was officially launched on November 2003 by the Acting Minister for Education, Mr. Tharman Shanmugaratnam. It covers the floors of Blk. S3 level 2 to 4 and includes the X-ray crystallography and cryo-EM facility at Blk. S2 basement, the NMR facility in Chemical and Molecular Analysis Center (CMAC) as well as the IBM e-server cluster at the Department of Computational Sciences. In the open laboratory concept, the laboratories of several staff members who share similar research interests are located together. This concept enables staff members and their students to develop strong collaborative research.

The Lee Wee Kheng Structural Biology Laboratories
Established in 2002 and located in Blk. S3 level 4, these laboratories contain five open laboratories (three for NMR spectroscopy and two for X-ray crystallography) for structural biology research. Thanks to the generous donation by the Lee Hiok Kwee's family, the shared core facility laboratory is furnished with equipments such as stackable shakers, high speed centrifuges, autoclaves, AKTA FPLC, spectropolarimeter (Jasco 810 CD) and ITC that are necessary for protein sample preparation and analysis. The laboratories also contain two computer rooms providing space and facilities, e.g. SGI and Linux workstations, for NMR and X-ray data analysis and protein structure calculation.

The Protein and Proteomics Center
This major core facility, located at Blk. S3 level 3, was renovated in 2003. The main objective of the Centre is to house, maintain, and operate various state-of-the-art, high-end research equipment and facilities, particularly related to research in proteomics and protein chemistry. The Centre thus provides a number of pieces of equipment for use by research personnel at NUS, and also a number of specialized services in protein analysis. These include various types of chromatography systems for protein purification, a Circular Dichroism (CD) Spectropolarimeter, Ciphergen SELDI Protein Chip System, PDQuest Gel Imaging System, and a Gel Cutter. The Centre also provides interactive services in N-terminal protein sequencing, and Mass Spectrometry. The Mass Spectrometry Facility currently houses four Systems: API 360 Triple Quadrupole MS System; ABI Voyager MALDI-Tof MS, Waters/Micromass Q-Tof II MS, and ABI Proteomics Analyzer MALDI-Tof-Tof MS, of which the latter was installed in early 2004.

The Lee Hiok Kwee Functional Genomics Laboratories
Originally established in 2001, and at the time called the Functional Genomics Laboratories, these are located at BLK S3-L02. In 2004, these laboratories were renamed as the Lee Hiok Kwee Functional Genomics Laboratories, in honor of a generous donation by the Lee Hiok Kwee family towards cutting-edge research in the Life Sciences. These are the first laboratories to adopt the open laboratory and core facility concept where several principal investigators work together in a state-of-the-art shared facility that boasts the latest in genomics and proteomics research. These include the micro-arrayer and scanner, 2D gel electrophoresis systems, Protein Chip systems, etc. The laboratories continue to serve as a model of the open lab concept in other thematic laboratories established recently at DBS.

The IBM e-server Cluster
The National University of Singapore (NUS) has received an IBM Shared University Research (SUR) award to the Structural Biology Research Group. The IBM eServer pSeries 670 server with four 1.5GHz POWER4+ processors (to be upgraded to 8 CPUs) and GB of RAM enables
computing-intensive tasks such as MD simulation to be performed. The computer system is installed at the NUS Department of Computational Science. The NUS Structural Biology Research Group's proposed research programs using the new IBM eServer pSeries 670 server include: Automated 3-D Structure calculation from unassigned NMR data and web-based structure solution search for X-ray diffraction data, structure-assisted drug screening and design and simulation of protein folding.

NMR Spectrometers and X-ray Image Plate Diffraction System
The recently installed Bruker 800MHz ultra-shielded ultrastabilized NMR spectrometer provides unprecedented sensitivity and resolution that is necessary for structural study of larger proteins. This $4.2 million equipment is funded by the Office of Life Science and is the first one in South East Asia. Besides the 800MHz NMR, the Department of Biological Sciences also has access to two Bruker AVANCE 500 MHz Nuclear Magnetic Resonance (NMR) spectrometers in the Chemical and Molecular Analysis Center at the Department of Chemistry. One of the 500 MHz NMR was upgraded with a 4-channel cryoprobe for high-resolution protein structure determination. DBS has a fully-equipped state-of-the-art X-ray crystallography facility that is located in the block S2 Level 1. The facility includes: R-axis IV+ area detector, Rigaku Xray generator with mirror optics, Cryo-cooling liquid nitrogen system, a computer to control diffraction data collection and processes the collected data. In addition, X-ray crystallography facilities accessible by the Department of Biological Sciences at the Institute of Molecular and Cell Biology provide another means of high esolution protein structure determination. A Nonius DIP2030 Imageplate detector mounted on the FR591 rotating anode X-ray generator allows rapid diffraction data collection of field proven quality.

Cryo-Electron Microscopes
The coordinated application of high-resolution cryoelectron microscopy and three-dimensional image reconstruction techniques enables acquisition of lowresolution structure of very high molecular weight molecules such as virus particles and membrane proteins. Electron Microscopes (EMs) function exactly as their optical counterparts except that they use a focused beam of electrons, electromagnetic lenses and vacuum instead of light and optical lenses to 'image' the specimen and gain information as to its structure and composition. DBS hosts fully-equipped state-of-the-art Electron Microscopes (Transmission and Scanning EMs) in the Electron Microscopy Laboratory at S2, basement. The facility includes: (1) JEOL JEM3010 HR TEM (magnification 1.2 million), with cold and heating holder; (2) JEOL JEM2010F (Field Emission gun, magnification 800K) with cryo holder; (3) PHILIPS CM10 (450K magnification) TEM; and (4) JEOL JSM T220A (35KV) SEM.