Laboratory of Biomolecular Structure and Function

Introduction: Three-dimensional structures of proteins determined by X-ray crystallography provide the atomic-scale detail needed to design better therapies to treat diseases and improve human health. After the discovery of the initial crystals for a protein of unknown structure, researchers often must optimize the diffraction quality of the crystals. This step requires testing many different conditions. The human proteins studied at OUHSC often have post-translational modifications that complicate protein preparation and crystallization. The Laboratory of Biomolecular Structure and Function (LBSF) provides a local source of X-ray diffraction instruments with cryosystems that shorten the crystal optimization step. The LBSF also provides help with protein expression, purification, crystallization, data collection with synchrotron radiation, small angle x-ray scattering studies, molecular modeling, and structure-based drug design. In addition, the LBSF interfaces with the BMB Physical Biochemisty Facility for further biophysical characterization of pure protein (ligand binding and thermal stability studies). 

Funding sources: The LBSF is supported by a combination of the OUHSC Office of the Vice President of Research, the OUSHC Department of Biochemistry and Molecular Biology, the NIH (via the OCSB and the Ok-INBRE), and user fees. The LBSF is funded in part by grants from the National Institutes of General Medical Sciences of the National Institutes of Health:
 
  1. National Institute of General Medical Sciences of the National Institutes of Health (Award No. P20GM103640 PI Ann West)
  2. National Institute of General Medical Sciences of the National Institutes of Health (Award No. P20GM103447 PI Darrin Akins)
Please acknowledge the LBSF and the above grants in the publications.
 

History: The Laboratory of Biomolecular Structure and Function (LBSF) was created in 2015 to serve the scientists of Oklahoma, in particular those at OUHSC and OMRF, that are interested in structural aspects of their macromolecular targets. It has been one of four core facilities in the Oklahoma Center of Biomedical Research Excellence (CoBRE) in Structural Biology (OCSB) since 2012. The LBSF has been part of the OUHSC Vice President Research Core Facilities since 2015. LBSF replaced the Macromolecular Crystallography Laboratory of the Biochemistry and Molecular Biology Department of OUHSC which was created in 1998.

X-ray diffraction: The laboratory itself is equipped with modern crystallographic equipment and computers: Rigaku 007 generator, R_axis IV and Mar345 image plate detectors, VariMax optics on both ports, Rigaku and Oxford Systems crystal cooling systems. The R-AXIS IV has an optional helium path for working with large unit cells. D-TrekXDSMosflm and HKL2000 image processing software are available for data processing. Any of PhenixCCP4CNS program suites can be used for structure determination and refinement, while COOTChimera, PymolVMD  and Molmol are offered for graphical representation of the results in 2D and 3D. 

Biophysical studies: A Wyatt plate-reading dynamic light scattering instrument enables high-throughput data collection with no user intervention for detection for the presence of aggregates, for evaluation of the  homogeniety of the sample, and for determining the oligomerization state in solution. This instrument is useful for screening samples and buffer conditions prior to crystallization experiments and other biophysical experiments that require a homogeneous sample such as small-angle X-ray scattering (SAXS), microcalorimetery, and microscale thermophoresis. 

Protein production: The LBSF oversees a Protein Expression and Purfication facility where users can overexpress and purify proteins on the miligram scale for crystallographic or other kinds of studies. Training in the use of the instruments is provided by Dr. Terzyan.

Molecular Modeling: Recently a Linux workstation with 4 GTX1080 GPUs (one GPU is equivalent of 138 CPUs) was purchased by the OCSB to carry out molecular dynamics simulations of macromolecules and other computationally intensive molecular modeling work. Available software includes AMBER16, Gromacs, and Rosetta software. 

Services

Laboratory provides following services:

Protein expression and purification (Dr. Terzyan):

  • design of constructs for protein expression
  • protein overexpression
  • protein purification

Crystallization services (Dr. Terzyan):

  • Crystallization experiment design and set-up.
  • Checking drops for crystals and acquiring their images.
  • Interfacing with the OU crystallization facility.
  • Dynamic light scattering data collection and analysis.

X-ray diffraction services (Dr. Terzyan):

  • Screening crystals for X-ray diffraction quality.
  • Optimization of Cryo protection solution.
  • X-ray data collection, processing and evaluation.
  • Structure determination, structure refinement, structure analysis.
  • Design of mutant proteins based on structural information.
  • Preparation of figures for grant applications and publication.
  • Preparation of files for printing 3d models of macromolecules.

Molecular modeling services (Dr. Mather):

  • Modeling of long range concerted molecular motion.
  • Structure-based ligand docking.
  • Structure-based rationale drug design.
  • Knowledge-based homology modelling.
  • Molecular dynamics simulation.

Main Users

Staff

Simon Terzyan PhD – Staff Scientist (BRC 406)

Timothy Mather PhD – Molecular Modeling Facility Director  (BRC 238)

Blaine Mooers PhD – LBSF Director (BRC 466)

Fees

$5.00/hour for x-ray data collection system                                                                          

$50.00/hour for assistance by Dr. Terzyan. Email Contact

$75.00/hour for assistance by Dr. Mather. Email Contact

Location

The LBSF is located in the Biomedical Research Center Building on the University of Oklahoma Health Sciences Center.

975 NE 10th Street
Biomedical Research Center Building, Room 406
Oklahoma City, Oklahoma 73104
(405) 271-8300
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