Physical Chemistry Seminar: Professor Song-I Han, UCSB

Physical Chemistry Seminar: Professor Song-I Han, UCSB (Host: Lynette Cegelski)

"Modulators of surface water dynamics from protein to silica surfaces"

About the Seminar

"The hydration water that solvates protein and lipid membrane surfaces is a major factor in driving or modulating biological events, including protein-protein and protein-ligand interactions, as well as the protonation of charged aminoacid residues. We investigate the role of the protein surface in modulating the hydration water fluctuations on both the picosecond and nanosecond timescale with an emerging experimental NMR technique known as Overhauser Dynamic Nuclear Polarization (ODNP). We carry out site-specific ODNP measurements of the hydration water fluctuations along the surface of Chemotaxis Y (CheY), and correlate the measured fluctuations to hydropathic and topological properties of the CheY surface. Furthermore, we compare hydration water fluctuations measured on the CheY surface to that of other globular proteins, as well as intrinsically disordered proteins, peptides, and liposome surfaces to systematically test characteristic effects of the biomolecular surface on the hydration water dynamics. Our results suggest that the labile (ps) and bound (ns) hydration water dynamics are modulated by the chemical topology of the surface, not only the geometrical topology as often assumed. Interestingly, the surface chemical topology also modulates the hydration of inorganic surfaces used in catalysis. On the example of silica with varying silanol coverage, we showcase the impact of surface chemical topology on surface hydration dynamics as measured by ODNP, that in turn alter the surface hydration force as measured by surface forces measurements."

About the Speaker

A concerted effort of my research group is the development of novel techniques and approaches, relying on electron and nuclear spin magnetic resonance that enables the study of biomolecular structure, dynamics and interaction with unprecedented sensitivity, resolution and information content. My lab takes a two-pronged approach: (1) to develop new instrumentation and methods, and (2) to pursue critical, outstanding, questions in biophysics whose resolution requires unconventional technical approaches and convincing new data. We are motivated by the power of “Seeing is Believing”. The direct experimental observation of dramatic conformational changes around signature hydrophobic regions of Tau when subject to aggregating conditions, offers a strong basis for the conformation-pathology hypothesis for Tau—an intrinsically disordered protein (IDP) implicated in devastating neurodegenerative diseases, including Alzheimer’s disease. The observation of water retardation at a liposome surface, reporting on the expected binding constant of a surface-active constituent upon titration proves surface adsorption, which is particularly meaningful if conventional signatures signifying binding such as calorimetric changes are absent. These are critical measurement capabilities, as weak biomolecular interactions are both prevalent and important in mediating protein function that are, however, difficult to capture. A core focus of my lab’s development is dynamic nuclear polarization (DNP) that amplifies the nuclear magnetic resonance (NMR) signal by several orders of magnitudes, by transferring polarization from highly polarized electron spin probes to the surrounding nuclei. We employ strategic spin probes at biomolecular sites or surfaces, and pursue ambient temperature Overhauser DNP of hydration dynamics at 10 GHz1-3, as well as solid-state magic angle spinning and static DNP NMR at 200 GHz at cryogenic temperatures4-5. Concurrently, we develop cw and pulsed electron paramagnetic resonance (EPR) capabilities at > 200 GHz and arbitrary waveform generation (AWG) pulsed EPR for the study of biomolecular structure and dynamics4, as well as utilize pulsed double electron electron resonance (DEER) methods.

1.    B.D. Armstrong, J. Choi, C. Lopez, D. A. Wesener, W. Hubbell, S. Cavagnero, S. Han, “Site-Specific Hydration Dynamics in the Nonpolar Core of a Molten Globule by Dynamic Nuclear Polarization of Water”, J. Am. Chem. Soc.133 (2011) 5987–5995. PMCID: PMC3095581.

2.    C. Cheng, J. Varkey, M.R. Ambroso, R. Langen, S. Han, “Hydration Dynamics as an Intrinsic Ruler for Refining Protein Structure at Lipid Membrane Interfaces”, Proc. Natl. Acad. Sci. 110 (42) (2013) 16838–16843. PMCID: PMC3800990.

3.    A. Schrader, S. Donaldson, J. Song, C. Cheng, D. Lee, S. Han, J. Israelachvili, “Correlating steric-hydration forces with water dynamics through surface force and diffusion NMR measurements in a lipid-DMSO-H2O system”, Proc. Natl. Acad. Sci. 112 (34) (2015) 10708–10713. PMCID: PMC4553805C.Y.

4.    I. Kaminker, R. Barnes, S. Han, “Arbitrary waveform modulated pulse EPR at 200 GHz”, J. Magn. Reson. 279 (2017) 81-90. PMCID: PMC5519772

5.    A. Leavesley, D. Shimon, T. Siaw, A. Feintuch, D. Goldfarb, S. Vega, I. Kaminker, S. Han, “Effect of electron spectral diffusion on static dynamic nuclear polarization at 7 Tesla”, Phys. Chem. Chem. Phys. 19 (2017) 3596-3605. PMID: 28094364