Thomas J. Magliery
|
Assistant Professor
(joint appointment with the Department of Chemistry)
Phone: 614-247-8425
Fax: 614-292-1685
email: magliery@chemistry.ohio-state.edu
Webpage: Magliery Homepage |
Research Interests:
Proteins adopt their conformations based on their sequence of amino
acids, but we still have little more than rules of thumb relating sequence
to structure or thermodynamic stability. In part, this is due to the
vast number of possible variants of even small proteins. Recently,
the advent of genomics and proteomics has massively increased the scale
of DNA and protein analysis, resulting in extremely rapid and inexpensive
DNA sequencing and large databases of sequence data on natural protein
variants.
We can now use the power of screens, selections and automation to analyze
large numbers of protein variants for foldedness, which we will use
to develop a deep, quantitative understanding of the relationship between
protein sequence and stability. We can also statistically analyze databases
of natural protein variants for higher-order patterns that lead to stability,
such as correlated occurrences of amino acids. The statistical results
of these analyses can then be tested rigorously by purifying protein
variants, measuring their stabilities and solving their structures.
Initial targets include the four helix bundle protein Rop and several
tumor suppressor proteins, stability defects in which lead to cancer.
We are also interested in using the recently developed power of in
vivo, site-specific unnatural protein mutagenesis to study difficult
problems in protein structure and interactions. For example, we are
developing a method to rapidly scan a photoaffinity label through every
position of a protein to elucidate binding partners and interaction
surfaces.
Publications
Selected publications from the last 5 years:
Magliery, T. J., Regan L. (2006) "Reassembled GFP: detecting protein-protein interactions and protein expression patterns." Methods Biochem Anal. 47, 391-405.
Magliery, T. J., Regan L. (2005) "Sequence variation in ligand binding sites in proteins." BMC Bioinformatics. 30;6, 240.
Magliery, T. J., Wilson CG, Pan W, Mishler D, Ghosh I, Hamilton AD, Regan L. (2005) "Detecting protein-protein interactions with a green fluorescent protein fragment reassembly trap: scope and mechanism." J Am Chem Soc. 127(1), 146-57.
Wilson CG, Magliery, T. J., Regan L. (2004) "Detecting protein-protein interactions with GFP-fragment reassembly." Nat Methods. 1(3), 255-62.
Magliery, T.J., Regan, L. (2004) “Beyond consensus: statistical
free energies reveal hidden interactions in the design of a TPR motif,”
J. Mol. Biol. 343, 731-745.
Magliery, T.J., Regan, L. (2004) “Combinatorial approaches to
protein structure and stability,” Eur. J. Biochem. 271, 1595-1608.
Magliery, T.J., Regan, L. (2004) “A cell-based screen for function
of the four-helix bundle protein Rop: A new tool for combinatorial experiments
in biophysics,” Protein Eng. Des. Select. 17, 77-83.
Anderson, J.C., Magliery, T.J., Schultz, P.G. (2002) “Exploring
the limits of codon and anticodon size,” Chem. Biol. 9, 237-244.
Magliery, T.J., Anderson, J.C., Schultz, P.G. (2001) “Expanding
the genetic code: selection of efficient suppressors of four-base codons
and identification of 'shifty' 4-base codons with a library approach
in Escherichia coli,” J. Mol. Biol. 307, 755-769.
