Fig 1.
(A) Structure of EBOV GP trimer in complex with the Ab100 antibody. GP1 is gray, GP2 is red and the heavy and the light chains of Ab100 are brown. (B) & (C) Mutations in the GP complex with ΔΔGBind > 2 kcal/mol (i.e., above black dashed line) are considered disruptive and are highlighted using green stick representation. (D) ΔΔGBind values (gray circles) for all 19 possible mutations at each site of GP1 (33–278) and GP2 (502–599). Different colors and counts in the legend indicate locations and number of mutations with ΔΔGBind > 2 kcal/mol on the GP complex.
Fig 2.
(A) Structure of EBOV GP trimer in complex with the Ab114 antibody. GP1 is gray, GP2 is red and the heavy and the light chains of Ab114 are orange. (B) Mutations in the GP complex with ΔΔGBind > 2 kcal/mol (i.e., above black dashed line) are considered disruptive and are highlighted using green stick representation. (C) ΔΔGBind values (gray circles) for all 19 possible mutations at each site of GP1 (33–278) and GP2 (502–599). Different colors and counts in the legend indicate locations and number of mutations with ΔΔGBind > 2 kcal/mol on the GP complex.
Fig 3.
(A) Structure of EBOV GP MLD peptide bound to the 13F6-1-2 antibody. GP MLD peptide is in gray tube representation, and the heavy and the light chains of 13F6-1-2 are black. Mutations in the GP MLD peptide with ΔΔGBind > 2 kcal/mol (i.e., above black dashed line) are considered disruptive and are highlighted using green stick representation. (B) ΔΔGBind values (gray circles) for all 19 possible mutations at each of the 11 sites of GP MLD peptide (404–414). Different colors and counts in the legend indicate locations and number of mutations with ΔΔGBind >2 kcal/mol on the GP complex.
Fig 4.
Maximum of folding stability, dimer binding stability (binding of GP1 and GP2) or trimer binding stability (binding of three GP1-GP2 complexes into a trimer of dimers), ΔΔGMax, as a function of ΔΔGBind for all antibody complexes.
ΔΔGMax values are considered to be zero for the intrinsically disordered 11-residue MLD peptide. Symbols in the inset legend indicate the corresponding antibody. Watch list mutations are shown as colored symbols and are predicted to disrupt binding to any one of the four antibodies (KZ52, Ab100, Ab114 and 13F6-1-2) but not to disrupt GP folding and trimer formation. Consistent with our previous study, mutations with ΔΔGBind > 2 kcal/mol are considered disruptive to antibody binding and those with −3 < ΔΔGMax < 3 kcal/mol are considered functional. The number of watch list mutations associated with each antibody is shown in the legend.
Table 1.
Watch list mutations.