Fayer Lab: Dynamics in Biological Systems

Dynamics in Biological Systems
Ilya Finkelstein and Aaron Massari

We are developing ultrafast multidimensional infrared spectroscopic methods and applying them to the study of protein dynamics in an entirely new manner. For the first time, we can investigate global protein structural evolution and describe how individual parts of a protein contribute to the dynamics. We have a broad mandate from the National Institute of Health to pioneer the application of ultrafast vibrational coherence methods to study a wide range of biological systems.

Multidimensional IR techniques are the ultrafast vibrational equivalent of the powerful methods used in multidimensional NMR. Rather than measuring the properties of nuclear spins, we can directly probe fluctuations in the protein structure and how it changes on the relevant molecular time scales. In collaboration with Roger Loring (Cornell University), we are gaining an atomistic understanding of protein dynamics by using molecular dynamics (MD) simulations to compliment our spectroscopic data.
Current efforts in our group have focused on elucidating the interdependence between a protein’s environment and dynamics. We have recently shown1 that ultrafast dynamics persist even when the protein is encapsulated in a glassy matrix.

Our results were in excellent qualitative agreement with MD simulations. Apparently, some protein fluctuations are nearly unaffected by the viscosity of the surrounding solvent!

The effect of molecular confinement on protein dynamics is another exciting area of research. In biological systems, proteins frequently perform their functions in nanometer length scale aqueous environments formed by the surrounding biological system. How nanoconfinement influences protein dynamics is important for understanding a wide variety of biological processes. Proteins can be encapsulated in sol-gel glasses where the pore size provides a nanoscopic aqueous medium. Proteins in nanoconfinement are speculated to exhibit damped structural fluctuations but there is little direct information. We are currently studying the dynamics of several proteins encapsulated in sol-gel glasses.
Next Steps

We are now using a heterodyne detection scheme for the vibrational echoes, which affords increased sensitivity and resolution. We are applying the methods to a variety of complex proteins and mutants. We are extending our studies to partially denatured states of proteins, activated and inhibited protein complexes, as well as real-time observation of structural interconversion in proteins and model compounds. For further information, please contact Michael Fayer, Ilya Finkelstein, or Aaron Massari.

Recent Publications

1.      Massari, A. M.; Finkelstein, I. J.; McClain, B.L.; Goj, A.; Wen, X.; Bren, K. L.; Loring, R. F.; Fayer, M. D. “The Influence of Aqueous versus Glassy Solvents on Protein Dynamics: Vibrational Echo Experiments and Molecular Dynamics Simulations.” J. Am. Chem. Soc. 2005. (accepted)

2.      Finkelstein, I. J.; Goj, A.; McClain, B.L.; Massari, A. M.; Merchant, K.; Loring, R. F.; Fayer, M. D. “Ultrafast Dynamics of Myoglobin without the Distal Histidine: Stimulated Vibrational Echo Experiments and Molecular Dynamics Simulations.” J. Phys. Chem. B. 2005. (accepted)

3.      McClain, B.L.; Finkelstein, I.J.; Fayer, M.D. “Dynamics of Hemoglobin in Human Erythrocytes and in Solution: Influence of Viscosity Studied by Ultrafast Vibrational Echo Experiments” J. Am. Chem. Soc. 2004, 126, 15702-15710.

4.      McClain, B.L.; Finkelstein, I.J.; Fayer, M.D. “Vibrational Echo Experiments on Red Blood Cells: Comparison of the Dynamics of Cytoplasmic and Aqueous Hemoglobin” Chem. Phys. Lett. 2004, 392, 324-329.

5.      Finkelstein, I.J.; McClain, B.L.; Fayer, M.D. “Fifth-Order Contributions to Ultrafast Spectrally Resolved Vibrational Echoes: Heme-CO Proteins” J. Chem. Phys. 2004, 121, 877-885.

6.      Merchant, K.A.; Noid, W.G.; Akiyama, R.; Finkelstein, I.J.; Goun, A.A.; McClain, B.L.; Loring, R.F.; Fayer, M.D. “Myoglobin-CO Substate Structures and Dynamics: Multidimensional Vibrational Echos and Molecular Dynamics Simulations” J. Am. Chem. Soc. 2003, 125, 13804-13818.