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PDBsum entry 1rog
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Histocompatibility antigen
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PDB id
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1rog
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DOI no:
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Biochemistry
33:11476-11485
(1994)
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PubMed id:
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Molecular dynamics simulation of MHC-peptide complexes as a tool for predicting potential T cell epitopes.
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D.Rognan,
L.Scapozza,
G.Folkers,
A.Daser.
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ABSTRACT
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The class I major histocompatibility complex-encoded HLA-B*2705 protein was
simulated in complex with six different peptides exhibiting unexpected
structure-activity relationships. Various structural and dynamical properties of
the solvated protein-peptide complexes (atomic fluctuations, solvent-accessible
surface areas, hydrogen bonding pattern) were found to be in qualitative
agreement with the available binding data. Peptides that have been
experimentally shown to bind to the protein remained tightly anchored to the MHC
molecule, whereas nonbinders were significantly more weakly complexes to the
protein and progressively dissociate from it at their N- and C-terminal ends.
The molecular dynamics simulations emphasize the unexpectedly important role of
secondary anchors (positions 1 and 3) in influencing the MHC-bound conformation
of antigenic nonapeptides. Furthermore, it confirms that dominant anchor
residues cannot solely account for peptide binding to a class I MHC molecule.
The molecular dynamics method could be used as a complementary tool to T cell
epitope predictions from the primary sequences of proteins of immunological
interest. It is better suited to MHC proteins for which a crystal structure
already exists. Furthermore, it may facilitate the engineering of T cell
epitopes as well as the rational design of new MHC inhibitors designed to fit
optimally the peptide binding cleft.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.A.King,
and
P.Bradley
(2010).
Structure-based prediction of protein-peptide specificity in Rosetta.
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Proteins,
78,
3437-3449.
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D.R.Flower,
K.Phadwal,
I.K.Macdonald,
P.V.Coveney,
M.N.Davies,
and
S.Wan
(2010).
T-cell epitope prediction and immune complex simulation using molecular dynamics: state of the art and persisting challenges.
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Immunome Res,
6,
S4.
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E.B.Unal,
A.Gursoy,
and
B.Erman
(2009).
Conformational energies and entropies of peptides, and the peptide-protein binding problem.
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Phys Biol,
6,
36014.
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R.Yaneva,
S.Springer,
and
M.Zacharias
(2009).
Flexibility of the MHC class II peptide binding cleft in the bound, partially filled, and empty states: A molecular dynamics simulation study.
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Biopolymers,
91,
14-27.
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D.S.DeLuca,
B.Khattab,
and
R.Blasczyk
(2007).
A modular concept of HLA for comprehensive peptide binding prediction.
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Immunogenetics,
59,
25-35.
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D.S.Deluca,
and
R.Blasczyk
(2007).
The immunoinformatics of cancer immunotherapy.
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Tissue Antigens,
70,
265-271.
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M.A.Joseph,
M.L.Mitchell,
J.D.Evanseck,
J.R.Kovacs,
L.Jia,
H.Shen,
and
W.S.Meng
(2007).
Secondary anchor substitutions in an HLA-A*0201-restricted T-cell epitope derived from Her-2/neu.
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Mol Immunol,
44,
322-331.
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A.J.Thompson,
P.L.Chau,
S.L.Chan,
and
S.C.Lummis
(2006).
Unbinding pathways of an agonist and an antagonist from the 5-HT3 receptor.
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Biophys J,
90,
1979-1991.
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P.Dönnes,
and
O.Kohlbacher
(2006).
SVMHC: a server for prediction of MHC-binding peptides.
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Nucleic Acids Res,
34,
W194-W197.
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P.Dönnes,
and
O.Kohlbacher
(2005).
Integrated modeling of the major events in the MHC class I antigen processing pathway.
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Protein Sci,
14,
2132-2140.
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L.Zhihua,
W.Yuzhang,
Z.Bo,
N.Bing,
and
W.Li
(2004).
Toward the quantitative prediction of T-cell epitopes: QSAR studies on peptides having affinity with the class I MHC molecular HLA-A*0201.
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J Comput Biol,
11,
683-694.
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M.Zacharias,
and
S.Springer
(2004).
Conformational flexibility of the MHC class I alpha1-alpha2 domain in peptide bound and free states: a molecular dynamics simulation study.
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Biophys J,
87,
2203-2214.
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P.L.Chau
(2004).
Water movement during ligand unbinding from receptor site.
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Biophys J,
87,
121-128.
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R.C.Hillig,
M.Hülsmeyer,
W.Saenger,
K.Welfle,
R.Misselwitz,
H.Welfle,
C.Kozerski,
A.Volz,
B.Uchanska-Ziegler,
and
A.Ziegler
(2004).
Thermodynamic and structural analysis of peptide- and allele-dependent properties of two HLA-B27 subtypes exhibiting differential disease association.
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J Biol Chem,
279,
652-663.
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PDB code:
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D.R.Flower
(2003).
Towards in silico prediction of immunogenic epitopes.
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Trends Immunol,
24,
667-674.
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I.A.Doytchinova,
P.Taylor,
and
D.R.Flower
(2003).
Proteomics in Vaccinology and Immunobiology: An Informatics Perspective of the Immunone.
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J Biomed Biotechnol,
2003,
267-290.
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H.Toh,
C.J.Savoie,
N.Kamikawaji,
S.Muta,
T.Sasazuki,
and
S.Kuhara
(2000).
Changes at the floor of the peptide-binding groove induce a strong preference for proline at position 3 of the bound peptide: molecular dynamics simulations of HLA-A*0217.
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Biopolymers,
54,
318-327.
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M.García-Peydró,
D.Rognan,
and
J.A.López de Castro
(2000).
Limited plasticity in the recognition of peptide epitope variants by an alloreactive CTL clone correlates directly with conservation of critical residues and inversely with peptide length.
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Tissue Antigens,
55,
289-295.
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N.Nagano,
E.G.Hutchinson,
and
J.M.Thornton
(1999).
Barrel structures in proteins: automatic identification and classification including a sequence analysis of TIM barrels.
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Protein Sci,
8,
2072-2084.
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S.Buus
(1999).
Description and prediction of peptide-MHC binding: the 'human MHC project'.
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Curr Opin Immunol,
11,
209-213.
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S.Dédier,
S.Krebs,
J.R.Lamas,
S.Poenaru,
G.Folkers,
J.A.López de Castro,
D.Seebach,
and
D.Rognan
(1999).
Structure-based design of nonnatural ligands for the HLA-B27 protein.
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J Recept Signal Transduct Res,
19,
645-657.
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F.García,
D.Rognan,
J.R.Lamas,
A.Marina,
and
J.A.López de Castro
(1998).
An HLA-B27 polymorphism (B*2710) that is critical for T-cell recognition has limited effects on peptide specificity.
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Tissue Antigens,
51,
1-9.
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S.Krebs,
J.R.Lamas,
S.Poenaru,
G.Folkers,
J.A.de Castro,
D.Seebach,
and
D.Rognan
(1998).
Substituting nonpeptidic spacers for the T cell receptor-binding part of class I major histocompatibility complex-binding peptides.
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J Biol Chem,
273,
19072-19079.
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C.Zhang,
J.L.Cornette,
and
C.Delisi
(1997).
Consistency in structural energetics of protein folding and peptide recognition.
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Protein Sci,
6,
1057-1064.
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D.Rognan,
L.Scapozza,
G.Folkers,
and
A.Daser
(1995).
Rational design of nonnatural peptides as high-affinity ligands for the HLA-B*2705 human leukocyte antigen.
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Proc Natl Acad Sci U S A,
92,
753-757.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
