Hanne Verswyvel

Chapter 4 │ Page 131 Figure 4: Protein flexibility is not significantly changed in the oxidized structures. The graphs show the RMSF of the residues of the native and oxidized ligands (i.e. HLA-Cw4 and HLA-E), averaged over the three replicas for each structure. Errors associated with sampling are shaded accordingly. Table 3. Secondary structure analysis of native and oxidized ligands (i.e. HLA-Cw4 and HLAE). The values given indicate the relative occurrence (in %) of di erent conformations. To investigate if the oxidation a ects the binding a inity of the investigated protein complexes, we performed pulling simulations followed by US simulations to determine the free energy profiles along the binding coordinate for each complex. One can see in Figure 5 that the oxidation of the ligands had minimal e ect on the profiles. The binding free energy, i.e. the depth of the potential well, was calculated to be -82 ± 4 kJ/mol for HLA-Cw4 – KIR2DL1 in its native form, changing to -89 ± 5 kJ/mol when oxidized. For the HLA-E – NKG2A/CD94 complex, the calculated binding energies of the native and oxidized forms are -138 ± 12 kJ/mol and -122 ± 19 kJ/mol, respectively. Our simulations thus predict that, given the errors associated with the energy profiles, both investigated ligands respectively have similar binding H H H H H H H H H

RkJQdWJsaXNoZXIy MTk4NDMw