Professor
Department of Biology
Krieger School of Arts & Sciences

ludwig.brand@jhu.edu

200 Mudd Hall
3400 N. Charles Street
Baltimore, MD 21218

Office: 410-516-7298
Lab: 410-516-7300

Our laboratory is interested in the dynamic structure and function of proteins, nucleic acids, glyco-conjugates, and membranes. Motions and interactions that occur on time scales from picoseconds to minutes are investigated. Fluorescence spectroscopy provides a relatively non-invasive probe and has the power to examine functional macromolecular assemblies both in solution and in the intact cell. Our main current interest is in the dynamics of induced motions in proteins. We are approaching this problem with the aid of time-resolved fluorescence emission studies. Nanosecond time-resolved spectral shifts of fluorescence emission may be related to the time dependence of the electric field around solvatochromatic fluorophores. We have investigated the tryptophan fluorescence of a number of proteins with only a single tryptophan and are able to interpret the nanosecond time-resolved measurements in terms of a relaxation of the protein matrix. The relaxation dynamics are faster for a small protein with a tightly packed core and slower for some larger proteins. We are interested in studying the relaxation dynamics of numerous proteins. Fluorescence spectroscopy is one of the few techniques capable of directly measuring the dynamics of nanosecond motions of protein segments. The dynamics of collective motions in proteins are almost certainly related to protein structure and function. Understanding this in different proteins is a main interest in the laboratory. Proteins being studied include, GB1, the B1 immunoglobulin-binding domain of Streptococcal protein G (in collaboration with the Knutson laboratory and the Gronenborn laboratory), IIAGlc of the PTS system (in collaboration with the Roseman laboratory), HIV protease (in collaboration with the Freire laboratory), Drosophila notch receptor (in collaboration with the Barrick laboratory), and Staphylococcal nuclease (in collaboration with the Garcia-Moreno E. laboratory).

Selected Publications
Toptygin, D., A.M. Gronenborn, and L. Brand. (2006) Nanosecond relaxation dynamics of protein GB1 identified by the time-dependent red shift in the fluorescence of tryptophan and 5-fluorotryptophan. J. Phys. Chem. B 110:26292-26302.

Xu, J., D. Toptygin, K.J. Graver, R.A. Albertini, R.S. Savchenko, N.D. Meadow, S. Roseman, P.R. Callis, L. Brand, and J.R. Knutson. (2006) Ultrafast fluorescence dynamics of tryptophan in the proteins monellin and IIAGlc. J. Am. Chem. Soc. 128:1214-1221.

Zheng, Y., F. Mamdani, D. Toptygin, L. Brand, J.T. Stivers, and P.A. Cole. (2005) Fluorescence analysis of a dynamic loop in the PCAF/GCN5 histone acetyltransferase. Biochemistry 44:10501-10509.

Toptygin, D., R.S. Savichenko, N.D. Meadow, and L. Brand. (2001) Homogeneous spectrally and time-resolved fluorescence emission from single-tryptophan of IIAGlc protein. J. Phys. Chem. B 105:2043-2055.

Toptygin, D., and L. Brand. (2000) Spectrally and time-resolved fluorescence emission of indole during solvent relaxation: a quantitative model. Chem. Phys. Lett. 322:496-502.