UNC-CH PhD Defense
Yuan Chong, UNC-CH
“NMR Studies of Protein Hydration and Protein-Ligand Interactions”
Hydration water plays a crucial role in a variety of biological processes such as protein folding and drug binding, but the underlying mechanism remains unclear. I employ an in-situ nuclear magnetic resonance (NMR) technique to study the mechanism of protein hydration and the role of hydration in alcohol-protein interactions. First, by measuring water isotherms on proteins at different temperatures, it is found that water interacts differently with hydrophilic and hydrophobic protein groups; hydration properties at hydrophobic groups undergo qualitative changes as temperature decreases below 10°C. Second, nanosecond to microsecond protein dynamics are studied as a function of hydration level and temperature. A crossover at 10°C in protein dynamics is found. The effect of water at hydrophilic groups on protein dynamics shows little temperature dependence, whereas water at hydrophobic groups has stronger effect above 10°C. Finally, alcohol-protein interactions are investigated as a function of hydration level. The free energy, enthalpy, and entropy of alcohol binding are also determined. Two types of alcohol binding are identified and the effect of hydration on alcohol binding is clearly revealed. These studies provide new insights into the nature of protein hydration and protein-ligand interactions, with implications for the understanding of protein function.