M.Sc. (Diplom-Physiker), 1996, Humboldt University, Berlin, Germany
Ph.D. (Dr. rer. nat.), 2000, Humboldt University, Berlin, Germany
Postdoctoral Fellow, 2001-2003, University of California, Berkeley (with Graham R. Fleming)
Using femtosecond laser spectroscopy, we are characterizing antibodies at different stages of their maturation to examine how binding specificity is evolved, which is a question of fundamental importance in biology with implications e.g. for autoimmunity and the evolution of antibiotic resistance. Binding specificity is also an important parameter of antibody therapeutics, and we are developing high-throughput assays to improve the specificity of antibody-based drugs.
Biochemical Applications of Modern Optical Spectroscopy
We develop biophysical techniques to study structure-function and dynamics-function relationships in proteins. This includes 3-photon echo peak shift spectroscopy (3PEPS) and related techniques to quantify the role of protein dynamics in molecular recognition. We are also developing novel infrared probes that can be incorporated into proteins and characterized using FTIR spectroscopy. To this end, we have pioneered the use of carbon-deuterium bonds as versatile and nonperturbative infrared probes of protein structure and dynamics.
We use stopped-flow mixing in combination with time-resolved FTIR to study chemical reaction dynamics. Time-resolved FTIR is an information-rich technique that can identify reaction intermediates and elucidate reaction mechanisms. We are focusing on mild metal-catalyzed C-H bond activation reactions, which have the potential to become a powerful tool in organic synthesis as a method for late-stage functionalization of complex organic molecules.
Adhikary, J. Zimmermann, R.L. Stanfield, I.A. Wilson, W.Yu, M. Oda, F.E. Romesberg: Structure and Dynamics of Stacking Interactions in an Antibody Binding Site, Biochemistry 58 (2019), 2987-2995.
Adhikary, J. Zimmermann, J. Liu, R.P. Forrest, T.D. Janicki, P.E. Dawson, S.A. Corcelli, F.E. Romesberg: Evidence of an Unusual N-H…N Hydrogen Bond in Proteins, J. Am. Chem. Soc. 136 (2014),13474-13477.
Zimmermann, M.C. Thielges, Y.J. Seo, P.E. Dawson, F.E. Romesberg: Cyano Groups as Probes of Protein Microenvironments and Dynamics, Angewandte Chem. Int. Ed. 50 (2011) 8333-8337.
Weinkam, J. Zimmermann, F.E. Romesberg, P.G. Wolynes: The Folding Energy Landscape and Free Energy Excitations of Cytochrome c, Acc. Chem. Res. 43 (2010) 652-660.
Zimmermann, E.L. Oakman, I.F. Thorpe, X. Shi, P. Abbyad, C.L. Brooks, S.G. Boxer, F.E. Romesberg: Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics. Proc. Natl. Acad. Sci. USA 103 (2006), 13722-13727.
B. Sagle, J. Zimmermann, P.E. Dawson, F.E. Romesberg: Direct and High Resolution Characterization of Cytochrome c Equilibrium Folding. J. Am. Chem. Soc. 128 (2006), 14232-14233.
Zimmermann, P.A. Linden, H.M. Vaswami, R.G. Hiller, G.R. Fleming: Two-Photon Excitation Study of Peridinin in Benzene and in the Peridinin Chlorophyll a-Protein (PCP). J. Phys. Chem. B 106 (2002), 9418-9423.