Crystallography and Computational Biosciences
Areas of Focus
Capabilities and Expertise
The Structural Biology team has
expertise in macromolecular crystallography and works with
investigators on all levels of structure determination.
- Consulting on all aspects of protein expression,
purification, and feasibility of structure determination.
- Identification of crystallization conditions and
possible other existing structures.
- Access to X-ray diffraction facility.
- Determination of the molecular structure through
Our Computational Biology expertise
lies in structure-based classical modeling, docking and analysis, but
additional expertise exists in computational biology/bioinformatics, and in
quantum mechanical calculations.
- Consultation to determine if the
problem is amenable to computation.
- Decide what sort of computations need to be performed.
- Calculations that we can readily
perform include: molecular dynamics, protein-protein docking, protein-ligand
docking, various bioinformatic analyses, reaction-diffusion modeling, quantum mechanical
calculations and other mathematical modeling may be possible.
Tools and Instruments Used
The X-ray facility houses a Rigaku
Micromax 007 X-ray source with dual VariMax-HF Confocal Optic Systems coupled
to Saturn92 CCD and RAXIS4+ detectors.
The systems are capable of cryogenic cooling for X-ray data
collection. The macromolecular
crystallization laboratory located next door is equipped with a Gryphon 96 well
crystallization robot (Art Robins Instruments), and all the necessary ancillary
equipment such as, microscopes and crystallization cabinets. The facility was
upgraded in 2012 with funds from the North Carolina Center for Biotechnology,
as part of its move to Wake Forest Biotech Place.
The computational facility contains
several multi-processor graphics workstations with hardware stereo for model
building and refinement. The facility
also houses a linux cluster with the appropriate software for computational
calculations such as molecular dynamics, in
silico drug docking and homology modeling. Intensive calculations and
molecular dynamics simulations are also made possible by access to the DEAC
computing cluster and GPU workstations.
Typical Areas Supported
The Crystallography and Computational
Biosciences Core supports areas of basic science research with an emphasis on
biological processes related to cancer such as cell signaling, transcriptional
regulation, DNA damage and repair, lipid metabolism, and redox regulation.
Some examples of recent
collaborations have been:
- Development of PI3K-kinase inhibitors.
- Development of fatty acid synthase inhibitors.
- Dissection of the molecular basis for peroxiredoxin
inactivation and repair by sulfiredoxin.
- Structure and function of the mammalian TREX1 3'
exonuclease and RNase H2 enzymes.