Group
Picture (October 2010)
Starring:
David Weliky as the faculty member –
Weliky CV
Matthew Nethercott as a graduate research associate
Scott Schmick as a graduate research associate
Erica Schwander as a graduate research associate
Li
Xie as a graduate research
associate
Koyeli
Banerjee as a graduate research
associate
Charles Gabrys
as a postdoctoral associate
Kelly
Sackett as a postdoctoral associate
FORMER GROUP MEMBERS
Yan Sun (Ph. D. 2009, currently a scientist in the Department
of Pharmacology and Molecular Sciences at Johns Hopkins
University)
Wei
Qiang (Ph. D. 2009, currently a
research associate in the Laboratory of Chemical Physics, National Institutes
of Health)
Jaime
Curtis-Fisk (Ph. D. 2009,
currently a scientist at Dow Chemical)
Matthew Gave (Ph. D. 2008, currently at scientist at Dow-Corning)
Zhaoxiong Zheng (Ph. D. 2007, currently a scientist in the Department
of Chemistry at Lehigh
University)
Angela Karst (currently a scientist at
American Litho)
Michele Bodner (Ph. D. 2006, currently a
scientist at Varian, Inc.)
Paul Parkanzky (Ph. D. 2006, currently a scientist at
Corium Corporation)
Rong Yang (Ph. D. 2005, currently a
scientist at Bristol-Myers Squibb)
Christian Canlas (Ph. D. 2004, currently a
NMR scientist in the Department of Chemistry, University
of California, Berkeley)
Jun Yang (Ph.
D. 2003, currently a research associate in the Department of Molecular
Cardiology, Lerner Research Institute, Cleveland Clinic)
Bhagyashree Khunte (M.
S. 2001, currently a scientist at Pfizer Corporation)
Contact Information
Dr. Weliky telephone:
517-355-9715 ext. 281
Graduate
Student/Post-doc telephone: 517-355-9715 ext. 282
Fax: 517-353-1793
Research
The Weliky group specializes in solid-state
NMR spectroscopy with particular application to biological systems and to
inorganic materials at high temperatures. Solid-state NMR is a powerful
approach to structural and dynamical measurements on biological molecules and
is particularly useful for studies in non-crystalline environments such as
membranes and bacterial inclusion bodies. We spend about 80% of our effort on
applications and 20% of our effort on new methods development. Our research
includes physical, analytical, organic, inorganic, and biological chemistries.
Applications
We are currently studying the structure of
the membrane-associated HIV gp41 envelope protein. One project focuses on the
fusion peptide region of gp41, which is required for viral/host cell membrane
fusion. We are studying this peptide as well as the whole gp41 protein in the
most biologically relevant membrane environment. Our goal is to better
understand the structural basis of membrane fusion which should be useful for
designing new AIDS therapeutics. We also have a related project on the
influenza virus fusion protein.
A second area is the structure of recombinant
proteins in bacterial inclusion bodies. Academic and pharmaceutical
laboratories commonly produce large quantities of a protein by introducing the
gene for this protein into E. coli
bacteria and having the bacteria make the protein. A common problem is
sequestration of the foreign protein in non-crystalline solids termed inclusion
bodies. Better understanding of the protein structure in inclusion bodies
should lead to better methods of obtaining useful protein from inclusion
bodies.
A third area is the mechanisms of syntheses
of inorganic compounds at high (600 oC) temperatures. Thousands of
inorganic compounds have been discovered with high-temperature synthesis but
the approach remains largely empirical in part due to the lack of information
about the species which exist at high temperature. We are addressing this
problem by doing the syntheses in the NMR spectrometer and taking NMR spectra
over the time courses of the reactions. The NMR spectra provide information
about the identities and concentrations of reactants, intermediates, and
products including their temporal variations.
Equipment
NMR
We have two 400 MHz Varian Chemagnetics
Infinity Plus spectrometers. In addition, we have a variety of magic angle
spinning and static probes. We also have time on a 900 MHz Bruker NMR at Michigan State University
for which there are magic angle spinning and static probes.
Biochemical
We have an ABI 431A peptide synthesizer,
incubator shaker, refrigerated centrifuges, preparative HPLC, uv-vis
spectrophotometer, and lyophilizer. We also have a nitrogen/vacuum line for
organic derivatization of amino acids.
Publications (in pdf format)
1.
E. P. Vogel, J. Curtis-Fisk, K. M. Young, and D.
P. Weliky, “Solid-State Nuclear Magnetic Resonance (NMR) Spectroscopy of Human
Immunodeficiency Virus gp41 Protein that includes the Fusion Peptide: NMR
Detection of Recombinant Fgp41 in Inclusion Bodies in Whole Bacterial Cells and
NMR Structural Characterization of Purified and Membrane-Associated Fgp41”, Biochemistry, 50, 10013-10026 (2011).
2.
K. Sackett, A. TerBush, and D. P. Weliky, “HIV
Six-Helix Bundle Constructs Induce Rapid Vesicle Fusion at pH 3.5 and Little
Fusion at pH 7.4: Understanding pH Dependence of Protein Aggregation, Membrane
Binding, and Electrostatics, and Implications for HIV-Host Cell Fusion”, European Biophysics Journal, 40, 489-502 (2011).
3.
S. D. Schmick and D. P. Weliky, “Major Antiparallel and Minor Parallel b Sheet
Populations Detected in the Membrane-Associated Human Immunodeficiency Virus
Fusion Peptide”, Biochemistry,
49, 10623-10635 (2010).
4.
S. Tristram-Nagle, R. Chan, E. Kooijman, P.
Uppamoochikkal, W. Qiang, D. P. Weliky, and J. F. Nagle, “HIV Fusion Peptide Penetrates, Disorders, and
Softens T-cell Membrane Mimics”, Journal
of Molecular Biology, 402, 139-153
(2010).
5.
I. Chung, D. Holmes, D. P. Weliky, and M. G.
Kanatzidis, “[P3Se7]3–: A Phosphorus-Rich
Square-Ring Selenophosphate”, Inorganic
Chemistry, 49, 3092-3094 (2010).
6.
K. Sackett, M. J. Nethercott, R. F.
Epand, R. M. Epand, D. R. Kindra, Y. Shai, and D. P. Weliky, “Comparative
Analysis of Membrane-Associated Fusion Peptide Secondary Structure and Lipid
Mixing Function of HIV gp41 Constructs that Model the Early Pre-Hairpin Intermediate
and Final Hairpin Conformations”, Journal
of Molecular Biology, 397,
301-315 (2010).
7.
C. M. Gabrys, R. Yang, C. M. Wasniewski, J. Yang, C.
G. Canlas, W. Qiang, Y. Sun, and D. P. Weliky, “Nuclear Magnetic Resonance Evidence
for Retention of Lamellar Membrane Phase with Curvature in the Presence of
Large Quantities of the HIV Fusion Peptide”, Biochimica et Biophysica Acta, 1798,
194-201 (2010).
8.
N. Huarte, J. L. Nieva, S. Nir and D. P. Weliky, “Induced
Perturbations and Adopted Conformations in Membranes by the HIV-1 Fusion
Peptide”, In Membrane-Active Peptides:
Methods and Results on Structure and Function, M. A. R. B. Castanho,
Editor, International University Line:La Jolla, 2009, pp. 565-596.
9.
I. Chung, J.-H. Song, M. G. Kim, C. D. Malliakas, A.
L. Karst, A. J. Freeman, D. P. Weliky, and M. G. Kanatzidis, “The Tellurophosphate K4P8Te4:
Phase-Change Properties, Exfoliation, Photoluminescence in Solution and
Nanospheres”, Journal of the
American Chemical Society, 131,
16303-16312 (2009).
10.
Y. Sun and D. P. Weliky, “13C-13C
Correlation Spectroscopy of Membrane-Associated Influenza Virus Fusion Peptide
Strongly Supports a Helix-Turn-Helix Motif and Two Turn Conformations”, Journal of the American Chemical Society,
131, 13228-13229 (2009).
11.
W. Qiang, Y. Sun, and D. P. Weliky, “A
Strong Correlation Between Fusogenicity and Membrane Insertion Depth of the HIV
Fusion Peptide”, Proceedings of the
National Academy of Sciences of the U.S.A., 106, 15314-15319 (2009).
12.
K. Sackett, M. J. Nethercott, Y.
Shai, and D. P. Weliky, “Hairpin Folding of HIV gp41 Abrogates Lipid Mixing
Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41
Constructs”, Biochemistry, 48, 2714-2722 (2009).
13.
W. Qiang and D. P. Weliky, “HIV Fusion Peptide and its Cross-Linked
Oligomers: Efficient Syntheses, Significance of the Trimer in Fusion Activity,
Correlation of b Strand Conformation with Membrane Cholesterol,
and Proximity to Lipid Headgroups”, Biochemistry,
48, 289-301 (2009).
14.
J. Curtis-Fisk, R. M. Spencer, and D. P.
Weliky, “Native Conformation at Specific Residues in Recombinant Inclusion Body
Protein in Whole Cells Determined with Solid-State Nuclear Magnetic Resonance
Spectroscopy”, Journal of the American
Chemical Society, 130,
12568-12569 (2008). – Featured in Chemical and Engineering News, 86, 31 (2008).
15.
J. Curtis-Fisk, R. M. Spencer, and D. P.
Weliky, “Isotopically Labeled
Expression in E. coli,
Purification, and Refolding of the Full Ectodomain of the Influenza Virus
Membrane Fusion Protein”, Protein
Expression and Purification, 61,
212-219 (2008).
16.
W. Qiang, M. L Bodner, and D. P. Weliky,
“Solid-State NMR Spectroscopy
of HIV Fusion Peptides Associated with Host-Cell-Like Membranes: 2D Correlation
Spectra and Distance Measurements Support a Fully Extended Conformation and
Models for Specific Antiparallel Strand Registries”, Journal of the American Chemical Society, 130, 5459-5471 (2008).
17.
M. A. Gave, K. M. Johnson, M. G.
Kanatzidis, and D. P. Weliky, “Improved Resolution and Detection of 31P-Tl
J-Couplings at 21 T in 31P Magic Angle Spinning Spectra of Inorganic
Compounds Containing Tl/Bi/P/S”, Solid
State Nuclear Magnetic Resonance, 33,
12-15 (2008).
18.
M. L. Bodner, C. M. Gabrys, J. O.
Struppe, and D. P. Weliky, “13C-13C and 15N-13C
Correlation Spectroscopy of Membrane-Associated and Uniformly Labeled HIV and
Influenza Fusion Peptides: Amino Acid-Type Assignments and Evidence for Multiple
Conformations”, Journal of Chemical
Physics, 128, 052319 (2008).
19.
Z. Zheng, W. Qiang, and D. P. Weliky,
“Investigation of Finite-Pulse Radiofrequency-Driven Recoupling Methods for
Measurement of Intercarbonyl Distances in Polycrystalline and
Membrane-Associated HIV Fusion Peptide Samples”, Magnetic Resonance in Chemistry, 45, S247-S260 (2007).
20.
C. M. Gabrys and D. P. Weliky, “Chemical
Shift Assignment and Structural Plasticity of a HIV Fusion Peptide Derivative
in Dodecylphosphocholine Micelles”, Biochimica
et Biophysica Acta-Biomembranes, 1768,
3225-3234 (2007).
21.
M. A. Gave, D. P. Weliky, and M. G. Kanatzidis,
“New Potassium Bismuth Thiophosphates Including the Modulated K1.5Bi2.5(PS4)3”,
Inorganic Chemistry, 46, 11063 -11074 (2007).
22.
I. Chung, J. I. Jang, M. A. Gave, D. P. Weliky,
and M. G. Kanatzidis, “Low Valent Phosphorus in the Molecular Anions [P5Se12]5–
and b-[P6Se12]4–:
Phase Change Behavior and Near Infrared Second Harmonic Generation”, Chemical Communications, 4998-5000
(2007).
23.
I. Chung, C. D. Malliakas, J. I. Jang, C. G.
Canlas, D. P. Weliky, and M. G. Kanatzidis, “Helical Polymer 1/¥[P2Se62–]:
Strong Second Harmonic Generation Response and Phase-Change Properties of its K
and Rb Salts”, Journal of the American
Chemical Society, 129,
14996-15006 (2007).
24.
M. A. Gave, C. G. Canlas, I. Chung, R. G.
Iyer, M. G. Kanatzidis, and D. P. Weliky, “Cs4P2Se10:
A New Compound Discovered with the Application of Solid State and High
Temperature NMR”, Journal of Solid State
Chemistry, 180, 2877-2884
(2007).
25.
J. Curtis-Fisk, C. Preston, Z. Zheng, R.
M. Worden, and D. P. Weliky, “Solid-State NMR Structural Measurements on the
Membrane-Associated Influenza Fusion Protein Ectodomain”, Journal of the American Chemical Society, 129, 11320-11321 (2007).
26.
W. Qiang, J. Yang, and D. P. Weliky,
“Solid-State Nuclear Magnetic Resonance Measurements of HIV Fusion Peptide to
Lipid Distances Reveal the Intimate Contact of b Strand Peptide with Membranes and the
Proximity of the Ala-14-Gly-16 Region with Lipid Headgroups”, Biochemistry, 46, 4997-5008 (2007).
27.
M. A. Gave, C. D. Malliakas, D. P. Weliky,
and M. G. Kanatzidis, “Wide Compositional and Structural Diversity in the System
Tl/Bi/P/Q (Q = S, Se) and Observation of Vicinal P-Tl J Coupling in the
Solid State”, Inorganic Chemistry, 46, 3632-3644 (2007).
28.
Z. Zheng, R. Yang, M. L. Bodner, and D. P.
Weliky, “Conformational Flexibility and Strand Arrangements of the
Membrane-Associated HIV Fusion Peptide Trimer Probed by Solid-State NMR
Spectroscopy”, Biochemistry, 45, 12960-12975 (2006).
29.
I. Chung, A. L. Karst, D. P. Weliky, and M.
G. Kanatzidis, “[P6Se12]4–: A Phosphorus-Rich
Selenophosphate with Low-Valent P Centers”, Inorganic
Chemistry, 45, 2785-2787 (2006).
30.
O. Palchik, R. G. Iyer, C. G. Canlas, D. P.
Weliky, and M. G. Kanatizidis, “K10M4M4¢S17
(M = Mn, Fe, Co, Zn; M¢ = Sn, Ge) and Cs10Cd4Sn4S17:
Compounds with a Discrete Supertetrahedral Cluster”, Z. Anorg. Allg. Chem.,
630, 2237-2247 (2004).
31.
R. Yang, M. Prorok, F. J.
Castellino, and D. P. Weliky, “A Trimeric HIV-1 Fusion Peptide Construct Which
Does Not Self-Associate in Aqueous Solution and Which Has Fifteen-Fold Higher
Membrane Fusion Rate”, Journal of the American Chemical Society, 126,
14722-14723 (2004).
32.
C. M. Wasniewski, P. D. Parkanzky, M. L. Bodner, and
D. P. Weliky, “Solid-State Nuclear Magnetic Resonance Studies of HIV and
Influenza Fusion Peptide Orientations in Membrane Bilayers Using Stacked Glass
Plate Samples”, Chemistry and Physics of Lipids, 132, 89-100
(2004).
33.
J. Yang, M. Prorok, F. J. Castellino, and D. P. Weliky,
“Oligomeric Structure of the Membrane-Bound HIV-1 Fusion Peptide Formed From
Soluble Monomers”, Biophysical Journal, 87, 1951-1963 (2004).
34.
I. Chung, J. Do, C. G. Canlas, D. P. Weliky, and M. G.
Kanatizidis, “APSe6 (A = K, Rb, and Cs): Polymeric Selenophosphates
with Reversible Phase-Change Properties”, Inorganic Chemistry, 43,
2762-2764 (2004).
35.
M. L. Bodner, C. M. Gabrys, P. D. Parkanzky, J. Yang, C.
A. Duskin, and D. P. Weliky, “Temperature Dependence and Resonance Assignment
of 13C NMR Spectra of Selectively and Uniformly Labeled Fusion
Peptides Associated with Membranes”, Magnetic Resonance in Chemistry, 42,
187-194 (2004).
36.
J. Yang and D. P. Weliky, “Solid State Nuclear Magnetic
Resonance Evidence for Parallel and Antiparallel Strand Arrangements in the
Membrane-Associated HIV-1 Fusion Peptide”, Biochemistry, 42,
11879-11890 (2003).
37.
R. J. DiCosty, D. P. Weliky, S. J. Anderson, and
E. A. Paul, “15N-CPMAS Nuclear Magnetic Resonance Spectroscopy and
Biological Stability of Soil Organic Nitrogen in Whole Soil and Particle-Size
Fractions”, Organic Geochemistry, 34, 1635-1650 (2003).
38.
C. G. Canlas, R. B. Muthukumaran, M. G.
Kanatzidis, and D. P. Weliky, “Investigation
of Longitudinal 31P Relaxation in Metal Selenophosphate Compounds”, Solid
State Nuclear Magnetic Resonance, 24, 110-122 (2003).
39.
C. G. Canlas, M. G. Kanatzidis, and D. P.
Weliky, “31P Solid State NMR Studies of Metal Selenophosphates
Containing [P2S6]4-, [P4S10]4-,
[PSe4]3-, [P2Se7]4-,
and [P2Se9]4- Ligands”, Inorganic
Chemistry, 42, 3399-3405 (2003).
40.
R. Yang, J. Yang, and D. P. Weliky, “Synthesis,
Enhanced Fusogenicity, and Solid State NMR Measurements of Cross-Linked HIV-1
Fusion Peptides”, Biochemistry, 42, 3527-3535 (2003).
41.
C. M. Gabrys, J. Yang, and D. P. Weliky, “Analysis of
Local Conformation of Membrane-Bound and Polycrystalline Peptides by
Two-Dimensional Slow-Spinning Rotor-Synchronized MAS Exchange Spectroscopy”, Journal
of Biomolecular NMR, 26, 49-68 (2003).
42.
J. Yang, P. D. Parkanzky, M. L. Bodner, C. G. Duskin, and D.
P. Weliky, “Application of REDOR Subtraction for Filtered MAS Observation of
Labeled Backbone Carbons of Membrane-Bound Fusion Peptides”, Journal of
Magnetic Resonance, 159, 101–110 (2002).
43.
K. K. Rangan, P. N. Trikalitis, C. Canlas, T.
Bakas, D. P. Weliky, and M. G. Kanatzidis, “Hexagonal Pore Organization in
Mesostructured Metal Tin Sulfides Built with [Sn2S6]4-
Clusters”, Nano Letters, 2, 513 – 517 (2002).
44.
J. A. Aitken, C. Canlas, D. P. Weliky, and
M. G. Kanatzidis, “[P2S10]4-: A Novel
Polythiophosphate Anion Containing a Tetrasulfide Fragment”, Inorganic Chemistry, 40, 6496-6498 (2001).
45.
J. Yang, C. M. Gabrys, and D. P. Weliky, “Solid State
Nuclear Magnetic Resonance Evidence for an Extended b Strand Conformation of the Membrane-Bound HIV-1 Fusion
Peptide”, Biochemistry, 40, 8126-8137 (2001).
46.
J. Yang, P. D. Parkanzky, B. A. Khunte, C. G. Canlas, R.
Yang, C. M. Gabrys, and D. P. Weliky, "Solid State NMR Measurements of
Conformation and Conformational Distributions in the Membrane-Bound HIV-1
Fusion Peptide", Journal of
Molecular Graphics and Modelling, 19, 129-135 (2001).
47.
J. J. Balbach, J. Yang, D. P. Weliky, P. J. Steinbach,
V. Tugarinov, J. Anglister, and R. Tycko, "Probing Hydrogen Bonds in the
Antibody-Bound HIV-1 gp120 V3 Loop by Solid State NMR REDOR Measurements",
Journal of Biomolecular NMR, 16, 313-327 (2000).
Courses
related to our work
Useful
Scientific Links
National
Magnetic Resonance Facility at Madison
Experimental
Nuclear Magnetic Resonance Conference
National
Institutes of Health Center for Research Resources
Center
for Advanced Biotechnology and Medicine - Protein NMR Spectroscopy Laboratory
Learn
or Teach NMR!
Michigan State
University.
Michigan
State University Department of Chemistry.
This is the place where we all work to improve the world.
The Chemistry
Department Brochure and Dr. Weliky’s brochure
page.
The Protein
Databank Page which stores information on the structure and composition of
proteins and DNA fragments.
Software and Freeware
RasMol,
a molecular display program.
Many of the pages here require Adobe Acrobat
to view them properly. If you do not have Adobe Acrobat, please go here.
If you
have comments or suggestions, email us at weliky@chemistry.msu.edu
This
page created on June 5, 1998 and last modified on November 27, 2010!