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

Table 2

Predicted changes of free energy changes (ΔΔ) of the four selected IFNγR1 variants with cavity-lining mutations relative to the wild type receptor. All energy values are in kcal/mol.

Variant	ΔΔ of folding of IFNγR1 in complex^*	ΔΔ of folding of free IFNγR1^†	ΔΔ of binding of IFNγR1/IFNγ complex^‡	Sequence conservation
V35L				80%
A114E				60%
D124N				40%
H222Y				40%

ΔΔ of folding of IFNγR1 bound to IFNγ measures the influence of mutations on the stability of the whole complex.
^†ΔΔ of folding of IFNγR1 alone represents changes of the stability of the isolated receptor.
^‡ΔΔ of binding of the whole complex between IFNγR1 and IFNγ estimates the change of the affinity between the receptor molecule and the rest of the complex.
Sequence conservation of amino acid residues at positions 35, 114, 124, and 222. It was based on the global alignment of 32 sequences of the extracellular part of IFNγR1 (Figure 2(c)).