Redesigning Protein Cavities as a Strategy for Increasing Affinity in Protein-Protein Interaction: Interferon-γ Receptor 1 as a Model

Figure 3

Color-coded values of free energy changes () of mutating the twelve cavity-lining residues of IFNγR1. values were calculated using the program FoldX for 500 MD snapshots and averaged. Red colored matrix fields indicate stabilization, blue ones destabilization. Shown are values calculated for PDB 1fg9 [19]; receptor chain C. analogical matrices are calculated for 1fg9 receptor chain D, and for receptor chains B and E from the structure 1fyh [20]. (1) “ of folding of IFNγR1 in complex” gauged the influence of mutations on the stability of the whole IFNγ/IFNγR1 complex. (2) “ of folding of free IFNγR1” estimated the effect of mutations on the stability of the isolated receptor. (3) “ of binding” of complex between IFNγR1 and IFNγ made an estimate of change of the interaction between the receptor molecule and the rest of the complex.