In this award, funded by the Experimental Physical Chemistry Program of the Division of Chemistry and the Molecular Biophysics Program of the Division of Molecular and Cellular Biosciences in the Biology Directorate, Professor Dongping Zhong of Ohio State University and his graduate and undergraduate research students are investigating the dynamical role of the hydration layer of water on a protein's structure, internal motion and function. They do this by combining femtosecond laser spectroscopic techniques with modern molecular biology techniques. Specific proteins to be studied include an alpha-helical globular protein and a beta-stranded globular protein.
The ultimate goal of the work by Professor Zhong and his group is to develop a fundamental chemical understanding of how a protein's motions are intimately influenced by the motions of the surrounding water molecules. With the kind of atomic and temporal resolution that are available in this study, the Zhong group hopes to obtain a better understanding of a variety of protein behaviors including protein recognition, folding, aggregation and enzyme catalysis. Along the way, Prof. Zhong hopes to build a strong, interdisciplinary program in physical biology at Ohio State and to train a new generation of researchers who are also strong teachers.
This project aimed to understand the dynamical role of water molecules around protein surfaces on affecting protein’s structure, dynamics and function by integrating ultrafast spectroscopy with temporal resolution of billionth of millionth of a second and molecular biology with a spatial resolution of a single protein residue, a central topic in protein science. Over the period of the grant, systematic studies of water motions around alpha-helical and beta-stranded globular proteins in different folding structures and in different thermal states have been characterized in real time using intrinsic amino-acid tryptophan as an optical probe to scan protein surfaces with site-specific mutagenesis. The results revealed the unique correlation of surface hydration water dynamics with protein structural and chemical properties in distinct protein architectures, the molecular mechanism of water-protein fluctuations, and the role of water motions in transition between alpha-helical and beta-stranded structures and in the physical origin of protein glass-type transition. The observed protein-associated water moves on the picosecond time scale (millionth of millionth of a second). The dynamics are found to be faster than protein fluctuations and slower than free bulk water motions, perfectly in the middle to link protein and bulk water in position and in time. These findings provide a thorough understanding of the ultrafast nature of hydration water dynamics, observed in the project, fundamental to many aspects of protein behaviors such as protein recognition, folding, aggregation and enzyme catalysis.
