|
The BMSD program provides an outstanding environment for training
and research in structural biochemistry and modern molecular biophysics.
We have particularly strong resources in X-ray crystallography, NMR,
laser spectroscopy, mass spectrometry, and molecular modelling and
computation. Brief descriptions of these resources are presented below.
Professors Niels Andersen, Patricia
Campbell, Rachel Klevit and Gabriele Varani constitute
the BMSD faculty in nuclear magnetic resonance.
A particular strength of the NMR group is the close integration
of solution and solid-state NMR methods for analysis of biological
systems. The facilities for NMR spectroscopy at the UW are first-rate,
and include the following modern instrumentation:
The 750 MHz NMR spectrometer housed in the Department
of Chemistry is unique in having two consoles from which experiments
can be run: a 4-channel Bruker DMX console with a 3-axis gradient
system for performing multidimensional solution NMR experiments,
and a multi-channel console, built in-house by Prof. Drobny
for solid-state NMR experiments. The main user groups of the
750 MHz spectrometer are members of the Molecular Biophysics
program (Profs. Campbell, Klevit and Varani).
There are currently five 500 MHz spectrometers at the University.
Several of these instruments have multi-channel consoles with
gradient capabilities and one has solid-state capabilities.
The newest addition at the University is a wide-bore 600 MHz
system for solid-state NMR applications. Niels Andersen's
group uses mainly a DRX 500 MHz spectrometer, which is equipped
with triple resonance probes.
The Department of Chemistry also has multiple lower-field NMR
spectrometers that are available for general use. The NMR facilities
in Chemistry are supported by a permanent staff member who assists
users (Dr. Joanna Long).
[top]
The BMSD faculty in protein
X-ray crystallography includes Adrian Ferré D'Amaré,
Jeff Foote, Wim Hol, Ethan Merritt, Ron Stenkamp, Barry Stoddard,
Roland Strong, David Teller and Wenqing Xu.
 
The Biomolecular Structure Center, which is
directed by Prof. Hol, has three fully equipped area detector
systems: (1) A Siemens X1000 multiwire detector system with a
four-circle goniometer, Oxford CryoStream cooling system and Rigaku
RU200 Rotating Anode; (2) an MSC RAXIS-II image plate system with
mirror options, an MSC cryocooling system and a RU-HR2 Rigaku
Rotating Anode; and (3) a MacScience DIP2030K image plate system
with Enraf Nonius Mirrors, MSC cryocooling system and Nonius FR591
rotating anode generator. For crystal growth and inspection there
are special rooms for crystal growth at room temperature, 4 C
and 11 C. Several microscopes are available for inspection of
crystallization trays and for mounting of crystals for data collection.
X-ray instrumentation at the FHCRC includes: (1) a Rigaku RU-200
rotating anode generator (12 kV, dual port) with Haskris 18 kW
heat exchanger; (2) an R-AXIS II phosphor storage plate area detector
(Molecular Structure Corporation) with adjustable 2-theta stage
that allows data collection on unit cells with dimensions up to
approximately 300 Å; (3) a Huber precession camera with
microscope and multiple linkage sets; and (4) a liquid nitrogen
cooling system that allows data collection from 200 to 20 C).
The University and FHCRC crystallographic faculty have excellent
access to synchrotron radiation sources, mainly at ALS and APS.
[top]
BMSD faculty whose work emphasizes computational
approaches include David Baker, Valerie Daggett, William Parson,
Ethan Merritt and Christophe Verlinde. Computers available in
the laboratories include numerous Silicon Graphics and Compaq/DEC-alpha
workstations and servers, Evans and Sutherland ESV graphics workstations,
and Beowolf clusters.
The Baker group's computing facilities include
approximately 500 production processors (CPUs), grouped roughly
into six clusters. Each cluster is a traditional Beowulf cluster
that takes full advantage of the parallel nature of methods
for predicting protein structure. The clusters are supported
by seven large file servers providing approximately five terabytes
of shared disk storage, and by a set of dedicated servers. This
system provides a reliable and robust distributed computing
environment for researchers in the group. The computers are
housed in two computing facilities, one located in the Department
of Biochemistry and the other in the central campus computing
center. These are joined by a gigabit encrypted VPN, allowing
for ready access to computing resources and data.
The molecular dynamics simulations by the Daggett group are
performed on two Beowolf clusters with a total of approximately
200 CPUs and 3 terabytes of disk space. The memory channel provides
very fast data transfer between machines and allows each CPU
to access all of the memory. The huge amounts of data generated
by the simulations are stored on optical disk drives and tape
backup facilities. The laboratory also has numerous personal
computers, graphics workstations and printers.
The crystallography and molecular modeling faculty in the Biomolecular
Structure Center have eight Silicon Graphics workstations, four
DEC Alpha servers including powerful three-processor ALPHA 4100
and ALPHA 2100 servers, eight X-terminals, and two Evans &
Sutherland ESV graphics workstations.
The computational facilities of the crystallography groups at
the FHCRC include: 19 graphics workstations (Silicon Graphics
and Athlon- and Intel-based Linux machines) for molecular modelling,
computations, detector control and data reduction; three compute
servers (a DEC Alpha and two dual processor Athlon XP Linux
machines); a dual processor Intel-based Linux file server with
a 540 Gbyte RAID-5 disk array; and numerous Macintosh and Windows
personal computers, printers, and tape drives. Two system administrators
maintain the UNIX cluster at no cost to the users.
The University and the FHCRC are networked via a fiber optic
backbone using Ethernet protocols. All trainees have accounts
on a large cluster of computers located in the Computing and
Communications Building (http://www.washington.edu/computing).
In addition to handling E-mail and Internet communications,
these computers provide Unix shells and extensive libraries
of software. Additional computational facilities are available
through the Locke Computer Center in the School of Medicine
(http://net.hs.washington.edu/locke/locke.html). The University
also is linked to the San Diego Supercomputer Facility, of which
we are a consortium member, and to other supercomputer facilities
around the country.
[top]
William Parson's research involves
laser optics and spectroscopy.
The Parson laboratory includes a home-built
Ti:sapphire laser system that provides near-IR pulses with widths
of under 20 fs. Excited samples can be probed with a timing
precision on the order of 1 fs. Changes in the transmission
of the probe pulses are measured by phase-sensitive lock-in
techniques or by a diode-array spectrometer. Extensive computer
code for data analysis is in place.
[top]
For characterizing protein folding and stability,
the Baker and Hol laboratories are equipped with an AVIV 62DS
circular dichroism machine, an AVIV 14 double beam spectrophotometer,
a Biologic stopped flow/quench flow machine, a scanning calorimeter,
a titration calorimeter, and a fluorimeter. In addition, the
Chemistry department has standard uv-vis spectrophotometers,
an FTIR spectrometer, and a Jasco J-720 spectropolarimeter for
circular dichroism spectroscopy.
[top]
[top]
Biophysical equipment in the Biomolecular Structure
Center includes: (1) a Brookhaven dynamic light scattering device
for determining particle size and homogeneity of protein solutions
prior to crystallization; and (2) a Spex
fluorimeter that is frequently used for tryptophan fluorescence
in proteins to determine thermostability and the affinity of
ligands.
For protein purification and characterization
the UW protein crystallography group has multiple chromatography
systems (Pharmacia FPLC, Perseptive Biosystem porous chromatography,
ISCO FOXY Jr., HP110 Series HPLC, and HPLC instrumentation equipped
with an Agilent ion-trap mass spectrometry detector), refrigerated
centrifuges, a Beckmann ultracentrifuge, an Elisa plate reader,
a Pharmacia Spectrophotometer, and a BioRad Biofocus 3000 capillary
llectrophoresis system.
The Electroscan Environmental Scanning Electron
Microscope facility in the Center for Bioengineering is used
by multiple groups to study structure in fully hydrated specimens.
The center also has a Balzers 360 freeze fracture instrument.
Shared facilities and instrumentation at the
FHCRC include multiple FPLC, HPLC, and perfusion chromatography
workstations, a dynamic light scattering workstation and diode
array spectrophotometer, five constant temperature incubators
for crystallization, a 30 L fermentation facility, metal and
electronics shops for fabrication and repair of small items,
and access to support from biocomputing and image analysis labs
for further computational and graphic analysis needs.
|
