Tuck C. Wong, Professor and Director of the Campus NMR Facility

BS, The Chinese University of Hong Kong, 1969
MS, University of Michigan, 1971
PhD, University of Michigan, 1974

Research areas

Biophysics, Interaction of HIV fusion peptides with membranes; NMR spectroscopy, molecular dynamics simulation, protein/peptide structure and dynamics.

(573) 882-7725; (573) 882-2754 (fax); e-mail: wongt@missouri.edu

 

 

 

 

Research Interests

Our research focuses on the concerted use of nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulation to study the interactions of peptides and proteins with model membranes, the structure and dynamics of the membrane-bound peptides/proteins and to understand the mechanism of peptide-receptor selection and recognition.

In NMR, multi-dimensional NMR is used to determine the conformation of the peptides/proteins in solution and in the "membrane-bound" form, and to determine the interactions of these molecules with the model membrane by making use of the intermolecular NOE and hydrogen bond patterns. Pulsed field gradient diffusion techniques are used to determine the partition and binding of the peptides/proteins into the membrane matrices. The determination of the temperature dependence of the partition enables the thermodynamics of the partition can be determined. In addition, the flexibility/motion of the membrane-bound peptides/proteins is studied by measuring the relaxation times (via H1-N15and H1-C13 HSQC). The changes in the mobility/flexibility of particular segment(s) of the peptide/protein upon incorporation into the membrane provide clues on which part(s) of the molecules interacts with the membrane.

MD simulations(using CHARMM or NAMD) of the peptides/proteins in explicit (all-atom) membrane models -- lipid micelles and bilayers -- provide information on the mode of binding of the peptides/proteins to the membrane (e. g. surface binding vs. insertion), the dynamics of the membrane-bound molecules (via the time correlation functions), and the specific interactions, such as hydrogen bonding, between the peptides/proteins with the membrane. Detailed analyses of the appropriate radial distribution functions reveal the distributions of the peptide backbone and the side-chains in the hydrophobic, interfacial and aqueous phases, respectively. The knowledge gained by these studies will shed light on the factors determining the binding of the peptides in the membrane. In addition, studies are being conducted to develop new MD methodology for this type of systems.

Selected Publications

Tuck C. Wong , "Membrane Structure of the Human Immunodeficiency Virus gp41 Fusion Peptide by Molecular Dynamics Simulation. II. The Glycine Mutants". Biochim. Biophys. Acta-Biomembranes (in press). [PDF]  [figures]

S. Kamath and Tuck C. Wong, "Membrane Structure of the Human Immunodeficiency Virus gp41 Fusion Domain by Molecular Dynamics Simulation", Biophys. J. 83, 135-145, 2002. (http://www.biophysj.org/cgi/content/full/83/1/135)[PDF]. [Figures].

Xinfeng Gao and T. C. Wong, "A Molecular Dynamics Investigation of the Structure and Dynamics of ACTH (1-10) peptides partitioned in a Dodecylphosphocholine (DPC) Micelle", Biopolymers, 58, 643-649, 2001. http://www3.interscience.wiley.com/cgibin/fulltext?ID=78003063&PLACEBO=IE.pdf

Gao X, Wong T. C. NMR studies of ACTH peptides in sodium dodecylsulfate and dodecylphosphocholine micelles. Proline isomerism and interactions of the peptides with micelles. Biopolymers. 58, 20-32, 2000. http://www3.interscience.wiley.com/cgi-bin/fulltext?ID=73502422&PLACEBO=IE.pdf

T. Wymore and T. C. Wong, "The Structure and Dynamics of ACTH(1-10) on the Surface of the Sodium Dodecylsulfate (SDS)Micelle: A Molecular Dynamics Simulation Study". J. Biomol. Struc. Dyn. 18, 461-476, 2000.

T. Wymore, X.-F. Gao and T. C. Wong, "Molecular Dynamics Simulation of the Structure and Dynamics of a Dodecylphosphocholine Micelle in Aqueous Solution", J. Mol. Struc. 1999, 485-486, 195-210. (The coordinates for the DPC micelle at 1203 ps are available with a crd or pdb file).

X.-F. Gao and T. C. Wong, "The Study of the Conformation and Interaction of Two Tachykinin Peptides in Membrane Mimicking Systems by NMR Spectroscopy and Pulsed Field Gradient Diffusion", Biopolymers, 1999, 50, 555-568.

T. Wymore and T. C. Wong, "Molecular Dynamics Study of Substance P Peptides Partitioned in an Sodium Dodecylsulfate Micelle", Biophysical J. 1999, 76,1213-1227. http://www.biophysj.org/cgi/reprint/76/3/1213.pdf

T. Wymore and T. C. Wong, "Molecular Dynamics Study of Substance P Peptides in a Biphasic Membrane Mimic", Biophysical J. 1999, 76, 1199-1212. http://www.biophysj.org/cgi/reprint/76/3/1199.pdf

X.-F. Gao and T. C. Wong, "Studies of the Partitioning and the Structure of Adrenocorticotropin (ACTH) Peptides in Membrane Mimics by Two-dimensional NMR and Pulsed Field Gradient Diffusion", Biophysical J. 1998, 74, 1871 - 1888. http://www.biophysj.org/cgi/reprint/74/4/1871.pdf

T. C. Wong, "One-Dimensional TOCSY and Related1D NMR Techniques", (a chapter in "Methods for Structure Elucidation by High Resolution NMR"), Elsevier, 1997.

K. F. Morris, C. S. Johnson, Jr., and T. C. Wong, "Diffusion Study of the Polymer-induced Non-Newtonian to Newtonian Transition in the Viscoelastic CTAB/ Sodium Salicylate/Water System by Two-Dimensional Diffusion Ordered Spectroscopy (DOSY)", J. Phys. Chem. 1994, 98, 603-608.

MD Simulation
Animation showing a1.763 ns MD simulation of an ACTH (1-10) peptide in a solvated DPC micelle
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