MRI: Acquisition of An Isothermal Titration Calorimeter for Studying Ligand-Macromolecule Interactions

点击翻译按钮获取中文摘要

This award is supported by the Major Research Instrumentation (MRI) and the Chemistry Research Instrumentation (CRIF) Programs. Professor Liang Xue from the University of the Pacific and colleagues Andreas Franz, Jerry Tsai and Xiaoling Li have acquired an isothermal titration calorimeter (ITC). This technique is used to determine the thermodynamic parameters of interactions in solution. The instrument consists of two cells enclosed in an adiabatic jacket that does not allow transfer of heat between the system being studied and its surrounding, thus the name isothermal meaning same temperature. Thermodynamics is the branch of chemical physics concerned with heat and temperature and their relation to energy and work. The calorimeter is used to study the binding and interaction of a ligand with a substrate. In one experiment the ligand is a small organic molecule and the substrate is DNA. The thermodynamics of the interaction is measured. Such binding data may be useful in investigating possible medicinal targets. The various research projects are undertaken by undergraduate students as well as high school students during the summer. Students from Delta College, a community college, are also being trained to use this modern instrumentation useful in the chemical and biochemical fields. The instrument is used in research and education at all levels, particularly by undergraduate students. It is being used to understand G4 ligands binding to G-quadruplex DNA which are secondary structures formed in nucleic acids by sequences rich in guanine. The instrument is also employed to validate the knob-socket protein packing statistical model which considers how protuberances fit into voids. The conformational changes of glycan and water liberation upon protein binding is being studied. Data are obtained to understand the structures of small molecules that stabilize the transport protein transthyretin that serves as carrier of the thyroid hormone. The instrument is also used in experiments designing peptides for targeting the epidermal growth factor receptor (EGFR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.