Zimmermann Lab

Molecular Immunology

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.

Selected Publications
* J. 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.
* J. Zimmermann, F.E. Romesberg, C.L. Brooks, I.F. Thorpe: Molecular Description of Flexibility in an Antibody Combining Site, J. Phys. Chem. B 114 (2010), 7359-7370.
* R. 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.

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.

Selected Publications
* J. 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.
* J. Zimmermann, K. Gundogdu, M.E. Cremeens, J.N. Bandaria, G.T. Hwang, M.C. Thielges, C.M. Cheatum, F.E. Romesberg: Efforts toward Developing Probes of Protein Dynamics: Vibrational Dephasing and Relaxation of Carbon-Deuterium Stretching Modes in Deuterated Leucine, J. Phys. Chem. B 113 (2009), 7991-7994.
* R. 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.

Reaction 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.