Office: KINSC E304B
Vibrational spectroscopy and conformational flexibility
My main research interest is the development of new physical techniques for understanding conformational flexibility and structural switching in proteins on a site-selected basis. The main instrumental techniques employed in my laboratory are infrared absorption spectroscopy and Raman scattering spectroscopy. We use the vibrational bands of native and modified amino acid side chains to determine the residue-level structural distribution and solvent exposure of proteins with particularly dynamic structures.
Conformational flexibility is intrinsic to a protein’s ability to function; if proteins were not floppy, they couldn’t do anything! For enzymes, limited flexibility allows them to capture, convert and release specific chemical targets. For proteins that are building blocks in larger structures, the ability of the building blocks to adopt multiple shapes can allow the construction of complex biomolecular assemblies. For proteins involved in signalling and regulation, structural flexibility allows them to bind to many different targets in different ways. The solvent is an important but often overlooked dynamic contributor to protein function. Vibrational spectroscopy is uniquely suited to observation of structural distributions and solvent dynamics, rather than just averaged and solvent-free protein structures. The techniques developed in my laboratory are being applied to understand the relationship between molecular flexibility and binding or self-assembly behavior in complexes made from multiple proteins and other biomolecular media: for example, viral capsids, multimeric enzymes, and membrane-bound proteins.
Haverford publications (*=undergraduates):
- Wolfshorndl, Marta P.*, Baskin, Rachel*, Dhawan, Ishita*, Londergan, C. H. Covalently bound azido groups are very specific water sensors, even in hydrogen-bonding environments. J. Phys. Chem. B, 2012, 116, 1172-1179. doi link.
- Alfieri, Katherine N.*, Vienneau, Alice R.*, Londergan C. H. Using infrared spectroscopy of cyanylated cysteine to map membrane binding structure and orientation of the hybrid antimicrobial peptide CM15. Biochemistry 2011, 50, 11097-11108. doi link.
- Bischak, Connor G.*, Longhi, Sonia, Snead, David M.*, Costanzo, Stephanie, Terrer, Elodie, Londergan, C. H. Probing structural transitions in the intrinsically disordered C-terminal domain of the measles virus nucleoprotein by vibrational spectroscopy of cyanylated cysteines. Biophys. J., 2010, 99, 1676-1683. doi link.
- Edelstein, Lena*, Stetz, Matthew G.*, McMahon, Heather A.*, Londergan, C. H. The effects of cyanylated cysteine and α-helical structure on each other. J. Phys. Chem. B, 2010, 114, 4931-4936. doi link.
- McMahon, Heather A.*, Alfieri, Katherine N.*, Clark, Katherine A. A.*, Londergan, C. H. Cyanylated cysteine: a covalently attached vibrational probe of protein-lipid contacts. J. Phys. Chem. Lett. 2010, 1, 850-855. doi link.
- Maienschein-Cline, Mark C.,* Londergan, Casey H. The CN stretching mode of aliphatic thiocyanate is sensitive to solvent dynamics and specific solvation. J. Phys. Chem. A 2007, 111, 10020-10025. doi link.
- Yang, Hailiu*, Habchi, Johnny, Longhi, Sonia, Londergan, C. H. Monitoring structural transitions in IDPs by vibrational spectroscopy of cyanylated cysteine. Methods in Molecular Biology, volume 895, 2012, pp. 245-270.
- NIH-AREA grant, 2012-2014.
- NIH-AREA grant, 2009-2011.
- Cottrell College Science Award from Research Corporation, 2009-2011.
- New Faculty Start-Up Award from the Camille and Henry Dreyfus Foundation, 2006-2011.