Bernhard Geierstanger, Ph.D.
Group Leader
Nuclear Magnetic Resonance (NMR) is established as one of the standard techniques in structural biology today, but it is not a static art. The field is constantly in motion as technologies advance and improve, and in our NMR Core Facility, we make use of the latest technology to provide core NMR services to GNF’s chemists (400 and 600 MHz) and to conduct cutting-edge research.
Microcoil NMR Spectroscopy
We have implemented an automated setup that allows injections of five microliter samples from 384-well plates into a capillary microcoil NMR probe. The platform is used for the quality control of compound collections, and we are exploring alternative applications such as screening for protein-ligand interactions and the detection of metabolites.
Protein-Ligand Binding Studies by NMR
At GNF, members of our NMR Core Facility work with scientists conducting molecular modeling, x-ray crystallography, and fragment-based screening to create synergy in identifying and optimizing drug leads.
We are also exploring how the incorporation of unnatural amino acids site-specifically into proteins can be utilized for NMR studies of protein structure and function and of protein-drug interactions in particular.
In collaboration with the Joint Center for Structural Genomics (http://www.jcsg.org/), we are applying NMR to the screening of metabolites for binding to Thermotoga maritima proteins. This helps to assign biochemical function to hypothetical proteins and is of general use for verifying and discovering functional annotations of enzymes. The approach will be applied to other proteomes in the future.
Structural Biology Studies by NMR
In collaboration with Professor Floyd Romesberg of The Scripps Research Institute (http://www.scripps.edu/chem/romesberg/) and our Structural Biology Group of GNF, we are investigating the effects of unnatural nucleobases on DNA structure.
Selected Publications
- Jansma A, Zhang Q, Li B, Ding Q, Uno T, Bursulaya B, Liu Y, Furet P, Gray NS, Geierstanger BH. Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy. J Med Chem 2007;50(24):5875-5877.
- Matsuda S, Fillo JD, Henry AA, Rai P, Wilkens SJ, Dwyer TJ, Geierstanger BH, Wemmer DE, Schultz PG, Spraggon G, et al. Efforts toward expansion of the genetic alphabet: structure and replication of unnatural base pairs. J Am Chem Soc 2007;129(34):10466-73.
- Jansma A, Chuan T, Albrecht RW, Olson DL, Peck TL, Geierstanger BH. Automated microflow NMR: routine analysis of five-microliter samples. Anal Chem 2005;77(19):6509-15.
- Deiters A, Geierstanger BH, Schultz PG. Site-specific in vivo labeling of proteins for NMR studies. Chembiochem 2005;6(1):55-8.
