Brief overview of Immunology
and Molecular Dynamics
Denise Chac
10 October 2014
Immunology
• The study of the human immune system
Lymphocytes
B Cells
• Membrane bound antibody
• Activation: bind to
pathogen and triggered by
helper T cells
• MHC II proteins present
antigen peptide on cell
surface
• Differentiates
– Effector Cells
– Memory Cells
T Cells
• T Cell Receptors (TCR)
• Helper T Cells
– Presents CD4
– Recognize MHC class II
– Activation: release of
cytokines
• Cytotoxic T Cells
– Presents CD8
– Recognizes MHC class I
– Destroys infected/cancerous
cells
B Cell
T-Cells
Viruses
HIV/AIDS
Previous Studies
• The breadth of epitope recognition within specific regions of
HIV antigen peptides contribute to anti-viral efficiency of CD8
T-cell response [Geldmacher et al. 2007]
• The altering of antigen peptides on MHC to give a more
‘protruding’ surface topology may increase TCR repertoire
diversity [Turner et al. 2005]
Method: Molecular Dynamics
• VMD – Visual Molecular Dynamics
– Program to visualize large biomolecular systems in 3-D
graphics
• Molecular Dynamics - NAMD
• MODELLER
– Homology studies
– Python based homology modeling software used for
modeling proteins
Methods: NAMD
• Parallel molecular
dynamics code
designed for highperformance simulation
of large biomolecular
systems
• Based on Charm++ but
can be compatible with
AMBER, CHARMM, and
X-PLOR
• Need:
– Protein Data Bank – PDB
• Atomic coordinates
• Velocities
– Protein Structure File – PSF
• Structural information
– Force Field Parameter File
• Mathematical potential of
atoms in the system
– Configuration File
• Tells how NAMD will run the
simulation
Methods: NAMD – the solvent
• Put protein in water to resemble the cellular
environment
• How?
– A water sphere in surrounding vacuum
• Without periodic boundary conditions
– A water box
• With periodic boundary conditions
Questions:
• “epitope enhancement”
• Difference between R5 and X4 HIV
• TCR flexibility [Martinez-Hackert et al. 2006]
References
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Martinez-Hackert, E., Anikeeva, N., Kalams, S.A., Walker, B.D., Hendrickson, W.A., Sykulev, Y., 2006.
Structural basis for degenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes.
Journal of Biological Chemistry 281, 20205–20212.
Geldmacher, C., Currier, J.R., Herrmann, E., Haule, A., Kuta, E., McCutchan, F., Njovu, L., Geis, S., Hoffmann,
O., Maboko, L., Williamson, C., Birx, D., Meyerhans, A., Cox, J., Hoelscher, M., 2007. CD8 T-cell recognition
of multiple epitopes within specific Gag regions is associated with maintenance of a low steady-state
viremia in human immunodeficiency virus type 1-seropositive patients. Journal of Virology 81, 2440–2448.
Turner, S.J., Kedzierska, K., Komodromou, H., La Gruta, N.L., Dunstone, M.A., Webb, A.I., Webby, R.,
Walden, H., Xie, W., McCluskey, J., Purcell, A.W., Rossjohn, J., Doherty, P.C., 2005. Lack of prominent
peptide–major histocompatibility com- plex features limits repertoire diversity in virus-specific CD8+ T cell
populations. Nature Immunology 6, 382–389.
Park, M., Park, S.Y., Miller, K.R., Collins, E.J., Lee, H.Y., 2013. Accurate Structure prediction of peptide-MHC
complexes for identifying highly immunogenic antigens. Molecular Immunology 56, 81-90.
Alberts, B., Johnson, A., Lewis, J. et al. 2002. Molecular Biology of the Cell. 4th Edition. New York: Garland
Science.
Janeway, C., Murphy, K., Travers, P., Walport, M. 2008. Janeway’s Immunobiology. 8th Edition. New York:
Garland Science .