Professor, Department of Biochemistry
Our work is centered on studying the structural and dynamical properties of proteins in order to understand the molecular mechanisms of protein function. We have developed new spectroscopic methods to obtain the vibrational spectra of specific protein groups and/or bound ligands, even within large proteins. With these techniques, it is possible to determine bond lengths with an accuracy of better than 0.01 Å. We also have developed techniques to monitor atomic motion in proteins on multiple time scales, as fast as picoseconds and out to minutes.
The primary problem of the lab is to understand the dynamics of enzymatic catalysis at a molecular level. This involves measurement of (1) static structures of enzymes complexes with their ligands and (2) how atomic motion evolves during the catalytic event. Structure is probed with vibrational spectroscopic tools that are capable of determining the Raman and IR spectra of bound substrates and specific protein molecular moieties. Vibrational spectroscopy yields a very high resolution of structure (better than 0.01 Å), and changes on this order are key to understanding enzymatic catalysis. The lab develops and applies advanced spectroscopic techniques as well as computational methods to understand how protein structure and dynamics determines function in proteins. We have worked extensively on several enzyme proteins. The idea is to understand the physics of atomic motion in proteins with a view that a deep understanding would lead to new classes of pharmaceuticals. The dynamics of protein folding is also an active area of study, that is how do proteins fold up into their functional three dimensional shapes. In fact the late dynamics of the protein folding problem is closely related to the dynamical nature of folded proteins.
"Active Site Loop Motion in Triosephosphate Isomerase: T-jump relaxation spectroscopy of thermal activation", Ruel Desamero, Sharon Rozovsky, Nick Zhadin, Ann McDermott, Robert Callender, Biochemistry 42, 2941-2951 (2003).
"Time-Resolved Approaches to Characterize the Dynamical Nature of Enzyme Catalysis", Robert Callender and R. Brian Dyer, Chemical Reviews 106, 3031-3042 (2006).
"Probing the Role of Dynamics in Hydride Transfer Catalyzed by Lactate Dehydrogenase", Nickolay Zhadin, Miriam Gulotta, and Robert Callender", Biophysical J. 95, 1974-1984 (2008).
"Ligand Binding and Protein Dynamics in Lactate Dehydrogenase", J. R. Exequiel T. Pineda, Robert Callender, and Steven D. Schwartz, Biophysical J. 93, 1474-1483 (2007)."Pyrophosphate Activation in Hypoxanthine-Guanine Phosphoribosyltransferase with Transition State Analogue", Hua Deng, Robert Callender, Vern Schramm, and Charles Grubmeyer, Biochemistry 49, 2705-2714 (2010).
"Conformational heterogeneity within the Michaelis complex of lactate dehydrogenase", Hua Deng, Dung Vu, Keith Clinch, Ruel Desamero, R. Brian Dyer, and Robert Callender, J. Phys. Chem. B. 115, 7670-6778 (2011).
“Investigation of Catalytic loop Structure, Dynamics, and Function Relationship of Yersina Protein Tyrosine Phosphatase by Temperature-Jump Relaxation Spectroscopy and X-ray Structural Determination”, Shan Ke, Meng-Chio Ho, Nickolas Zhadin, Hua Deng, and Robert Callender, J. Phys. Chem. B. 116, 6166-6176 (2012).
More Information About Dr. Robert Callender
Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Golding Building, Room 303
Bronx, NY 10461