Fig. 3: Stability and context-dependency.
From: Origins and breadth of pairwise epistasis in an α-helix of β-lactamase TEM-1
a Stability model. \({P}_{{nat}}\) is the probability that the protein folds. b Effects of the mutations on the stability. Black dotted line corresponds to \({P}_{{nat}}\). Red dot corresponds to the wild-type. Orange dot corresponds to a single mutation on the α-helix, with \(\Delta \Delta {G}_{i}^{a}\). Yellow dot corresponds to a single mutation on the α-helix, with \(\Delta \Delta {G}_{j}^{b}\)Blue dot corresponds to double mutations on the α-helix, with \(\Delta \Delta {G}_{i}^{a}+\Delta \Delta {G}_{j}^{b}\). Mutations are considered as additive in \(\Delta \Delta G\). However, this results in non-additive effect in \({P}_{{nat}}\). c The relationship between background log-fitness and mutant’s relative log-fitness predicted by the model of stability is presented. The protein modeled has a free energy of −4.55 kcal mol−1, and the impact of mutations, \(\Delta \Delta G\), is −2, −0.5, 0, 0.5, 2 and 3 kcal mol−1 from red to blue. d Histogram of the \(\Delta \Delta G\) estimated. Red line corresponds to \(\Delta {G}_{0}\). Black dashed line corresponds to \({P}_{{nat}}\) as a function of \(\Delta {G}_{0}+\Delta \Delta G\). Source data are provided as a Source data file.
