Figure legends:
Figure 1: Epistasis scatterplots for binding (A) and folding (B). Both figures use a cutoff of 0.5 kcal/mol and show data characterized as no epistasis (black), positive epistasis (blue), and negative epistasis (red).
Figure 2: Observed epistasis as a function of alpha-carbon separation between mutation sites for binding (A) and folding (B). Black indicates no-epistasis using our cutoff of 0.5 kcal/mol, and blue and red indicate positive and negative epistasis, respectively.
Figure 3: (A) Comparison between the alternative (left) and null (right) models for epistatic effect, ϵ , as a function of separation distance, r . Results of log(likelihood) ratio test for separation distance with 1000 samples for simulated data for binding affinity (B) and folding stability (C). These plots show the alternative model is a significantly better explanation of the data than the null model.
Figure 4: Comparison of binding model of epistasis for the categories of charge (A) and complex type (B). The mean value for a given subcategory is indicated by a black dot. The barplots show the histograms within the categories. In parenthesis is the number of mutation pairs belonging to each category. For the complex type, the number of complexes belonging to each category are shown in square brackets.