PMID- 1511679
OWN - NLM
STAT- MEDLINE
DCOM- 19920929
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 208
IP  - 1
DP  - 1992 Aug 15
TI  - Molecular dynamics study of a complex between the human histocompatibility 
      antigen HLA-A2 and the IMP58-66 nonapeptide from influenza virus matrix protein.
PG  - 101-13
AB  - The structure of the influenza-virus-matrix-protein (IMP) 58-66 nonapeptide, 
      bound to the major-histocompatibility-complex-encoded human leukocyte antigen 
      (HLA) A2 protein was studied by molecular dynamics simulation. Starting from the 
      extra electron density map of peptides co-crystallized with HLA-A2, the 
      nonapeptide IMP58-66 was docked residue by residue in the protein binding cleft. 
      The complex was simulated for 100 ps in a shell of 1372 water molecules. The 
      averaged simulated HLA-A2 conformation was found to be similar to the crystal 
      structure (0.182 nm RMS deviation, for the backbone atoms of the alpha 1-alpha 2 
      domain). Nine out of the 14 hydrogen bonds observed in the antigen-binding site 
      were reproduced in the simulation. The IMP58-66 peptide exhibits an extended 
      conformation with kinks at positions 3 and 5. The side chains of residues 2, 3 
      and 9 develop van der Waals' interactions with hydrophobic pockets of HLA-A2, 
      corresponding to polymorphic residues of the 
      major-histocompatibility-complex-encoded proteins. Both the N-terminus and 
      C-terminus of the nonapeptide were anchored in the antigen-binding groove by 
      hydrogen bonds with conserved amino acids. The N-terminus was more flexible and 
      contacts four HLA-A2 conserved tyrosines (Tyr7, Tyr59, Tyr159 and Tyr171) and 
      Glu63 by direct or water-relayed hydrogen bonds. Water intercalation occurred 
      only around the N-terminus of the peptide, the C-terminal carboxylate forming 
      strong hydrogen bonds with polar residues (Tyr84 and Thr143) and a salt bridge 
      with Lys146 all over the molecular dynamics simulation. This model is fully 
      compatible with the recently published crystal structure of the HLA-B27 protein, 
      complexed by a mixture of self nonapeptides.
FAU - Rognan, D
AU  - Rognan D
AD  - Department of Pharmacy, Swiss Federal Institute of Technology, Zurich.
FAU - Zimmermann, N
AU  - Zimmermann N
FAU - Jung, G
AU  - Jung G
FAU - Folkers, G
AU  - Folkers G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - 0 (Viral Matrix Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - HLA-A2 Antigen/*chemistry/metabolism
MH  - Humans
MH  - Hydrogen Bonding
MH  - Kinetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Orthomyxoviridae/*metabolism
MH  - Peptide Fragments/chemistry/metabolism
MH  - Protein Conformation
MH  - Software
MH  - Time Factors
MH  - Viral Matrix Proteins/*chemistry/metabolism
EDAT- 1992/08/15 00:00
MHDA- 1992/08/15 00:01
CRDT- 1992/08/15 00:00
PHST- 1992/08/15 00:00 [pubmed]
PHST- 1992/08/15 00:01 [medline]
PHST- 1992/08/15 00:00 [entrez]
AID - 10.1111/j.1432-1033.1992.tb17163.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1992 Aug 15;208(1):101-13. doi: 
      10.1111/j.1432-1033.1992.tb17163.x.