Aizhuo Liu Research Interests
Dr. Liu's research interests are in the characterization of structure, dynamic, and intermolecular interaction of proteins and protein/nucleic acid complexes through the use of NMR spectroscopy as a major technique to obtain biologically and chemically relevant information on their behaviors. My research includes the development of more efficient solution NMR experimental methods and the use of them to obtain information on three-dimensional atomic structures of biomacromolecules, particularly integral membrane proteins, molecular structure-function relationships, location and time scales of dynamic processes, location and kinetics of ligand interactions, and the effects of solvent conditions on the conformations of the biomacromolecules. I am also interested in the application of new NMR parameters and techniques to the characterization of molecular recognition and protein/small molecule interactions, which is critical information for drug development.
In parallel to running the MSU Biomolecular NMR Facility, I am conducting the following research projects:
1.) Solution NMR study of integral membrane proteins. Membrane proteins play critical roles in many cellular and physiological processes and represent 70% of the targets for drug development. Despite of their biological significance, structural information on membrane proteins is scarce. The paucity of the structural information on membrane proteins is a major hindrance to the understanding of their functions and the development of new medicines. Dr. Honggao Yan of our Department and I are jointly developing integral membrane protein systems for the solution NMR study. We choose multi-drug transporters as model systems. Multi-drug transporter-mediated extrusion of drugs is one of major problems in chemotherapeutic treatment of cancers and infectious diseases. Knowledge about the structure-function relationships in multi-drug transporters is urgently needed for addressing the problem of multi-drug resistance.
2.) New NMR parameters and techniques for large molecular and supramolecular systems. NMR is an ever-developing technique for the structural and dynamic study of biomacromolecules. New trends of NMR technique development have been towards the structure determination of even larger systems, including integral membrane proteins, and the extraction of new parameters for the structural and dynamic characterizations. One of my focuses in this area is the direct detection of hydrogen bonds in a macromolecule and between molecules in a complex. Information on hydrogen bond networks is very important for the study of enzyme catalysis and molecular recognition. The introduction of a 900 MHz NMR instrument on MSU campus through the Michigan Life Science Corridor should provide us with a unique facility to conduct method development for this purpose.
3.) Advanced NMR techniques for drug development. NMR is one of most important techniques in drug development and has been used in many stages in the process, from compound screening, structural characterization of both small ligand molecules and large protein targets, to lead generation and modification. One of my efforts is to develop new NMR methods, such as 19F-NMR techniques, for the improvement of the efficiency of compound screening and the enhancement of the information on molecular structure, dynamics, and intermolecular interactions.