Nuclear Magnetic Resonance of Biological Systems

David Weliky


41 CEM


Research webpage

Primary Research Area

Physical (Ph)

Other Area(s) of Interest

Analytical (An)

Biological (Bi)

Chemical Physics (CP)

Inorganic (In)

Material (Ma)


(Research Description PDF)

Nuclear magnetic resonance (NMR) spectroscopy in the solid state is a powerful approach to determine atomic-resolution structure and motion in systems for which the molecules do not rapidly tumble. Our research focuses on application of solid-state NMR to problems in membrane fusion, bacterial inclusion bodies, and inorganic materials.

Membrane Fusion: Fusion between cells and cellular components has an essential role in living organisms for such significant physiological processes as egg fertilization and synaptic transmission in the nervous system. Membrane fusion is also an important step in HIV and influenza viral infection of human cells and is mediated by proteins in the viral membrane that bind to the target cell membrane during infection. We are using solid-state NMR to determine the conformations, membrane locations, and oligomerization states of the membrane-bound HIV and influenza viral fusion proteins and using these data to develop an atomic-resolution structural model of fusion protein-induced membrane fusion.


(Top) Normal E. coli cell. (Bottom) E. coli cell that has produced recombinant protein. The dark regions in the right panel are inclusion bodies.


Bacterial Inclusion Bodies: Proteins for fundamental research or therapeutic purposes are usually produced by putting the DNA which codes for the protein into E. coli bacteria, culturing the bacteria to high densities, and then inducing production of the “recombinant” protein. Most of the recombinant protein is usually sequestered in non-crystalline solids in the bacterial cytoplasm that are termed “inclusion bodies” and which are viewed negatively by researchers because typical solubilization protocols for inclusion bodies are denaturing with the subsequent requirement of refolding whose success is variable and dependent on the specific protein. Because there is little molecular-level structural information on inclusion body protein, we are carrying out solid-state NMR studies with a particular emphasis on inclusion bodies in whole bacterial cells. One overall goal is development of non-denaturing solubilization protocols for inclusion body protein.

While doing this research, students learn a variety of skills which could include peptide synthesis, protein expression and purification, design and repair of NMR equipment, NMR theory and pulse sequence development, and computer simulation. Our research is benefiting from the enhanced sensitivity and resolution of the 900 MHz NMR spectrometer at MSU.


Selected Publications

Full-Length Trimeric Influenza Virus Hemagglutinin II Membrane Fusion Protein and Shorter Constructs Lacking the Fusion Peptide or Transmembrane Domain: Hyperthermostability of the Full-Length Protein and the Soluble Ectodomain and Fusion Peptide Make Significant Contributions to Fusion of Membrane Vesicles, P. U. Ratnayake, E. A. Prabodha Ekanayaka, S. S. Komanduru, and D. P. Weliky, Protein Expr. and Purif. 2016, 117, 6-16.

Closed and Semiclosed Interhelical Structures in Membrane vs Closed and Open Structures in Detergent for the Influenza Virus Hemagglutinin Fusion Peptide and Correlation of Hydrophobic Surface Area with Fusion Catalysis, U. Ghosh, L. Xie, L. Jia, S. Liang, and D. P. Weliky, J. Am. Chem. Soc. 2015, 137, 7548-7551.

REDOR Solid-State NMR as a Probe of the Membrane Locations of Membrane-Associated Peptides and Proteins, L. Jia, S. Liang, K. Sackett, L. Xie, U. Ghosh, and D. P. Weliky, J. Mag. Reson. 2015, 253, 154-165.

Multiple Locations of Peptides in the Hydrocarbon Core of Gel-Phase Membranes Revealed by Peptide 13C to Lipid 2H Rotational-Echo Double-Resonance Solid-State Nuclear Magnetic Resonance, L. Xie, L. Jia, S.Liang, and D. P. Weliky,  Biochemistry 2015, 54, 677-684. Highlighted on Biochemistry website.

Folded Monomers and Hexamers of the Ectodomain of the HIV gp41 Membrane Fusion Protein: Potential Roles in Fusion and Synergy Between the Fusion Peptide, Hairpin, and Membrane-Proximal External Region, K. Banerjee and D. P. Weliky,  Biochemistry 2014, 53, 7184-7198.

NMR Spectroscopy of the HIV gp41 Membrane Fusion Protein Supports Intermolecular Antiparallel b Sheet Fusion Peptide Structure in the Final Six-Helix Bundle State, K. Sackett, M. J. Nethercott, Z. Zheng, and D. P. Weliky, Journal of Molecular Biology 2014, 426, 1077-1094.

Quantitation of Recombinant Protein in Whole Cells and Cell Extracts via Solid-State NMR Spectroscopy, E. P. Vogel and D. P. Weliky,  Biochemistry 2013, 52, 4285-4287. Highlighted on Biochemistry website


B.A., 1985, Swarthmore College

Ph.D., 1995, Univ. of Chicago

Postdoctoral Fellow, 1995-97, National Institutes of Health.


1998 New Faculty Award Camille and Henry Dreyfus Foundation
1996 NIH Fellows Award for Research Excellence National Institutes of Health
1995 - 1997 Postdoctoral Research Fellow National Institutes of Health
1995 Ph.D. The University of Chicago
1992 Research Fellow AT&T Bell Laboratories
1991 - 1995 AT&T Ph.D. Scholar AT&T
1988 - 1991 NSF Predoctoral Fellow National Science Foundation
1987 - 1991 McCormick Fellow
1985 Bachelor of Arts with High Honors in Chemistry and Physics Swarthmore College
1985 Member Sigma Xi Honor Society (Swarthmore College)
1985 Phi Beta Kappa Phi Beta Kappa (Swarthmore College)
1981 - 1982 N. Harvey Collisson Scholar Swarthmore College
1981 - 1985 National Merit Scholar