MIT Chemistry Directory

Mei Hong


Research in the Hong laboratory lies at the interface of physical chemistry and biological chemistry. We develop and apply high-resolution solid-state NMR spectroscopy to determine the atomic structures and dynamics of biological macromolecules. On the methodological side, we develop new multidimensional correlation NMR experiments and analysis approaches to measure interatomic distances from angstroms to nanometers, elucidate the geometry of molecular motions from sub-nanoseconds to seconds, and determine intermolecular binding. We not only detect 1H, 13C and 15N NMR spectra but also observe 19F, 31P and 2H spins, which allow us to investigate a broad range of chemical and biophysical problems. Our solid-state NMR techniques increasingly integrate fast magic-angle-spinning (MAS), 1H detection, high magnetic fields, and dynamic nuclear polarization to enhance the sensitivity of structure determination.

Using these NMR approaches, we are studying three classes of biomolecular systems: virus membrane proteins, amyloid fibrils, and plant cell walls. In the membrane protein direction, we are investigating the influenza M2 protein family and viral fusion proteins. Influenza M2 is a proton channel as well as a membrane-scission protein: the first function initiates virus uncoating while the second function mediates virus budding and release. Antiviral drugs that target the M2 proton channel activity are currently limited by the circulation of resistant M2 mutants among influenza A viruses and the lack of effective blockers against influenza B M2. We are studying fundamental aspects of proton transport in these channels, especially how protein conformational dynamics and water mediate proton transfer, and how the amino acid sequence and the lipid environment affect proton-transfer equilibria and kinetics. To elucidate how M2 causes membrane scission, we are studying M2 interactions with cholesterol and other virus proteins. In a second membrane protein project, we investigate fusion proteins of enveloped viruses, including paramyxovirus and HIV. These fusion proteins merge the virus envelope with the target cell membrane to cause virus entry. Using solid-state NMR, we determine the protein structures at different stages of virus-cell fusion and couple the observed conformational changes with membrane curvature, which is detected by 31P NMR and other biophysical methods. Results from these studies are giving detailed insights into how these fusion proteins coordinate with lipids to cause membrane merger.

In the second direction, we are investigating the structures and assemblies of amyloid fibrils, including fibrils involved in Alzheimer’s disease, fibrils formed from peptide hormones, and fibrils designed for catalysis. We are particularly interested in understanding how the amino acid sequence dictates the three-dimensional folds of amyloid fibrils, the origin of molecular structural polymorphism, how water impacts fibril formation, and how metal ions stabilize amyloid fibrils.

In the third direction, we bring multidimensional solid-state NMR to bear on the energy-rich material of plant cell walls. Plant cell walls comprise of a complex mixture of polysaccharides and proteins. By 13C-enriching whole cell walls, we are able to employ a variety of 2D and 3D 13C and 1H correlation NMR techniques to determine the composition, conformation, intermolecular interaction, and mobilities of the polysaccharides. Intact cell walls of both dicot and grass families are being studied. Of particular interest are how the structures of cellulose microfibrils in plant cell walls differ from crystalline cellulose of bacteria and algae, and how the polysaccharide network is loosened during rapid plant growth. Our findings have implications for how to harvest energies from lignocellulose materials.

Contact Information

t: 6172535521


NW14-3212 ; 6-223



Administrative Assistant

Jillian Haggerty
Tel: (617) 253-5478
Room NW14-3218
77 Massachusetts Ave.
Cambridge, MA 02139