Research Synopsis: Our group utilizes theoretical and computational tools to elucidate the structure, dynamics and spectroscopy of biological systems.
Our group utilizes theoretical and computational tools to elucidate the structure, dynamics and spectroscopy of biological systems.
Theoretical vibrational spectroscopy of biomolecules. Linear and non-linear vibrational spectroscopy has been widely used to probe biomolecules, such as proteins and DNAs, due to the sensitivity of specific normal modes to the underlying molecular structure and dynamics. Our research focuses on developing theoretical schemes that accurately and efficiently predict the spectral features of biomolecules based on their structure and dynamics, which bridge molecular dynamics simulations and spectroscopy experiments. Our methods will enable the interpretation of complex experimental spectra at the atomic level and allow for the prediction of distinct spectral changes in biological processes that can be validated by experiments. The techniques of interest include linear and 2D IR, Raman and sum-frequency generation spectroscopy.
Strong hydrogen bonds in biological systems. Hydrogen bonds with very short donor-acceptor heavy atom distances (R < 2.6 Å) are commonly observed in proteins. The close proximity of the heavy atoms results in a unique electrostatic environment in the protein interior and modulates the ionization of amino acid side chains. In addition, shortening R can lead to proton delocalization between the hydrogen bonding partners by making the barrier of proton transfer comparable to the zero point energy of the O-H or N-H bond. Our research aims to elucidate the structure, dynamics and functional roles of these short hydrogen bonds, for which we will use a hierarchy of techniques ranging from simulations with classical force fields and methods that explicitly include the quantum nature of both the electrons and nuclei.
- L. Wang, S. D. Fried, S. G. Boxer and T. E. Markland, “Quantum delocalization of protons in the hydrogen bond network of an enzyme active site”, Proc. Natl. Acad. Sci., 111, 18454 (2014)
- L. Wang, M. Ceriotti and T. E. Markland, “Quantum fluctuations and isotope effects in ab initio descriptions of water”, J. Chem. Phys., 141, 104502 (2014)
- J. K. Carr, L. Wang and J. L. Skinner, “Theoretical sum frequency generation spectroscopy of peptides”, J. Phys. Chem. B, 119, 8969 (2015)
- L. Wang, L. E. Buchanan, E. B. Dunkelberger, J. J. de Pablo, M. T. Zanni and J. L. Skinner, “Ultrafast infrared spectroscopy of amylin solution and fibrils”, Chapter 14 in Ultrafast Infrared Vibrational Spectroscopy, Editor: M. D. Fayer, CRC Press (2013)
- L. Wang and J. L. Skinner, “Thermally induced protein unfolding probed by isotope-edited IR spectroscopy”, J. Phys. Chem. B, 116, 9627 (2012)
- A. M. Woys, A. M. Almeida, L. Wang, C.-C. Chiu, M. McGovern, J. J. de Pablo, J. L. Skinner, S. H. Gellman and M. T. Zanni, “Parallel β-sheet vibrational couplings revealed by 2D IR spectroscopy of an isotopically labeled macrocycle: Quantitative benchmark for the interpretation of amyloid and protein infrared spectra”, J. Am. Chem. Soc., 134, 19118 (2012)
- L. Wang, C. T. Middleton, S. Singh, A. S. Reddy, A. M. Woys, D. B. Strasfeld, P. Marek, D. P. Raleigh, J. J. de Pablo, M. T. Zanni and J. L. Skinner, “2DIR spectroscopy of human amylin fibrils reflects stable β-sheet structure”, J. Am. Chem. Soc., 133, 16062 (2011)
- L. Wang, C. T. Middleton, M. T. Zanni and J. L. Skinner, “Development and validation of transferable amide I vibrational frequency maps for peptides”, J. Phys. Chem. B, 115, 3713 (2011)
- A. S. Reddy, L. Wang, S. Singh, Y. L. Ling, L. Buchanan, M. T. Zanni, J. L. Skinner and J. J. de Pablo, “Stable and metastable states of human amylin in solution”, Biophys. J., 99, 2208 (2010)
- A. S. Reddy, L. Wang, Y.-S. Lin, Y. Ling, M. Chopra, M. T. Zanni, J. L. Skinner and J. J. de Pablo, “Solution structures of rat amylin peptide: Simulation, theory, and experiment”, Biophys. J., 98, 443 (2010)