computer modeling in molecular biology.pdf

7 Major Histocompatibility Complex Class I Protein-Peptide Interactions 209Figure 7-18. Overlay of five conformers (displayed in magenta, red, purple, green and cyan)from the simulation of the Arg-P2 residue of the EBNA 3C peptide in the “45-pocket” ofHLA-B*2705. It may be clearly observed that TIP451 is stationary throughout the simulation.The movements of the Arg-P2 side chain are small and are co-operative with those of TIP456,a water residue which is involved in the square planar hydrogen bonding network in the P2pocket .(Colour illustration see page XVI).4 Figure 7-17. Overlay of the initial and final conformers of the EBNA 3C peptide. Initial conformersare coloured dark-grey and final conformers are coloured light-grey.(a) The EBNA 3C complexed to HLA-B*2702 demonstrating the different conformations ofGluP8 and the movement of water molecules around position 77 and 80.(b) Top view of the EBNA 3C peptide as complexed to HLA-B*2702. The conformationtermed C1 in the text is represented by the dark-grey side chain at P8. The C2 conformationis represented by the light grey side chain. Slight movements of the peptide backbone appearto have occured due to the movement of water molecules in the “bed” underneath the peptide.(c) Orthologous view to (a) for the interaction of the EBNA 3C peptide with HLA-B*2705.The movement of water molecules in the simulation of these two alleles may be directly contrastedbetween the two figures.(d) Orthologous view for (b) for the interaction of the EBNA 3C peptide with HLA-B*2705.In contrast to the different distribution of water molecules around the peptide in the cleft ofthe two isotype molecules it may be observed that the peptide has a highly similar conformationin the two environments, suggesting that it is the movement of solvent within the cleftof the isotype molecules which allows for cross-reactivity of this peptide.