The Crystallography and Computational Biosciences (CCB) Shared Resource serves as a portal for access to:
- State-of-the-art X-ray crystallographic equipment
- Technical support
- High-performance computing
- Scientific consultation for Cancer Center researchers
The CCB meets the growing needs for structure determination and computational analysis of protein and DNA/RNA structure, function and dynamics for a diverse array of projects ranging from basic science questions to drug design.
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
We provide access to cutting-edge modeling and simulation methods. The information from these complementary approaches can be used to develop novel therapies, as it’s essential for assessing and exploiting the biological function of the target protein.
The CCB also provides support for ongoing projects and the development of new projects through the collection of preliminary data for funding applications.
Capabilities and Expertise
Our structural biology team has expertise in macromolecular crystallography and works with investigators on all levels of structure determination.
Some examples of recent collaborations include:
- 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
Program Key: CPC = Cancer Prevention and Control Program; CRP = Clinical Research Program; TPR = Tumor Progression and Recurrence Program; CBB = Cancer Biology and Biochemistry Program
Huhn AJ, Parsonage D, Horita DA, Torti FM, Torti SV, Hollis T. The high molecular weight kininogen domain 5 is an intrinsically unstructured protein and its interaction with ferritin is metal mediated. Protein Sci. 2014;23: 1013-22. PMC4116651.
Fye JM, Coffin SR, Orebaugh CD, Hollis T, Perrino FW. The Arg-62 residues of the TREX1 exonuclease act across the dimer interface contributing to catalysis in the opposing protomers. J Biol Chem. 2014;289: 11556-65. PMC4036290.
Stuart CH, Horita DA, Thomas MJ, Salsbury FR, Jr., Lively MO, Gmeiner WH. Site-specific DNA-doxorubicin conjugates display enhanced cytotoxicity to breast cancer cells. Bioconjug Chem. 2014;25(2): 406-13. PMC3983131.
Negureanu L, Salsbury FR, Jr. Non-specificity and synergy at the binding site of the carboplatin-induced DNA adduct via molecular dynamics simulations of the MutSalpha-DNA recognition complex. J Biomol Struct Dyn. 2014;32: 969-92. PMC3884054.
Godwin R, Gmeiner W, Salsbury FR, Jr. Importance of long-time simulations for rare event sampling in zinc finger proteins. J Biomol Struct Dyn. 2015: 1-10. PMC4600012.
Lu Y, Salsbury FR, Jr. Autoinhibitory mechanisms of ERG studied by molecular dynamics simulations. AIP Adv. 2015;5(1): 017130. PMC4387600.
Cunniff B, Newick K, Nelson KJ, Wozniak AN, Beuschel S, Leavitt B, Bhave A, Butnor K, Koenig A, Lowther WT, James AM, et al. Disabling mitochondrial peroxide metabolism via combinatorial targeting of peroxiredoxin 3 as an effective therapeutic approach for malignant mesothelioma. PLoS One. 2015;10(5): e0127310 PMC4444329.
Davis RR, Shaban NM, Perrino FW, Hollis T. Crystal structure of RNA-DNA duplex provides insight into conformational changes induced by RNase H binding. Cell Cycle. 2015;14(4): 668-73 PMC4615118