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.

We also wish to understand how proteins arrive at their three dimensional structure (the protein folding problem). A number of studies are underway to understand the thermodynamics of folding. In addition, the crucial kinetic events of protein folding occur faster than the conventional millisecond time scale of stopped-flow mixing techniques. The early kinetic events (down to nanoseconds) in the folding process are being studied using advanced techniques that initiation chemistry on fast time scales.

• "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).
• “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).
• “Large Scale Dynamics of the Michaelis Complex of B. Stearothermophilus Lactate Dehydrogenase revealed by Single Tryptophan Mutants Study”, Beining Nie, Hua Deng, Ruel Desamero, Robert Callender, Biochemistry 52, 1886-1892 (2013).
• “Energy Landscape of the Michaelis Complex of Lactate Dehydogenase: relationship to catalytic mechanism”, Hua Deng, Ho-Lei Peng, Michael Reddish, R. Brian Dyer, Robert Callender, Biochemistry 53, 1849-1857 (2014).
• “Direct Evidence of Catalytic Heterogeneity in Lactate Dehydrogenase by Temperature Jump Infrared Spectroscopy”, Michael Reddish”, Huo-Lei Peng, Hua Deng, Kunal Panwar, Robert Callender, R. Brian Dyer, J. Phys. Chem. B 118, 10854-10862 (2014).  PMC4167064
• "Mechanisms of Thermal Adaptation in the Lactate Dehydrogenases", Huo-Lei Peng, Tsuyoshi Egawa, Eric Chang, Hua Deng, Robert Callender, J. Phys. Chem. B 119, 15256-15262 (2015).  PMC4679558
• “The Dynamical Nature of Enzymatic Catalysis”, Robert Callender and R. Brian Dyer, Accounts of Chemical Research 48, 407-413 (2015).  PMC4333057.
• “Resolution of sub-millisecond kinetics of multiple reaction pathways for lactate dehydrogenase”, Reddish, M., Callender, R. H., and Dyer, R. B., Biophysical J. 112, 1852-1862 (2017). PMC5425397
• "Thermodynamic and structural adaptation differences between mesophilic and psychrophilic lactate dehydrogenases", Khrapunov, Sergei, Chang, Eric, and Robert Callender, Biochemistry 56, 3587-3595 (2017).  PMC5574168