Chapter 4 │ Page 129 larger (fluctuations in) RMSD. The oxidized versions of the simulated MHC-I complexes converge to an RMSD that is on average higher than the native structures. For HLA-Cw4 – KIR2DL1, the RMSD of the oxidized structure converges to an average value of 0.52 nm (averaged over the three replicas), compared to 0.38 nm for the native structure, while for HLA-E – NKG2A/CD94, the average converged RMSD is 0.44 nm for the oxidized structure, compared to 0.32 nm for the native structure, indicating that the oxidized proteins indeed equilibrated to a di erent conformation. On the other hand, the RMSD fluctuations do not exhibit a clear di erence, which indicates that the flexibility of the ligands is not a ected to a large degree by the oxidative changes. This is supported by the calculated RMSF of the ligands, as shown in Figure 4. For HLA-E, the RMSF is nearly unchanged after oxidation. For HLA-Cw4, the RMSF of the oxidized system is slightly higher in some regions, particularly near the oxidized residues, indicating a slightly increased local flexibility. Notably, the native HLA-Cw4 was calculated to already be more flexible than HLA-E. While the RMSD of both simulated MHC-I complexes suggests they undergo a change in conformation after NTP-induced oxidation, they almost completely retain their secondary structure. Analysis of the secondary structure of the ligands is shown in Table 3. In the case of HLA-Cw4, the most prominent alteration in the secondary structure is a decrease in the turn structure, accompanied by an increase in random coil structures. For HLA-E, the most notable change in secondary structure is a slight decrease in the helical structure, again accompanied by an increase of random coils. Visual inspection indicated that this change is caused by denaturation of the helix between residues 49 and 54, likely as a result of the two tryptophan oxidations (Trp51 and Trp60) in this region. Visual inspection also revealed that the most notable conformational change of the oxidized proteins compared to their native structure is a pivot of the ligand with respect to the domain that binds to the receptor. This occurs for both simulated
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