Region neighboring wildtype sequences where <i>P</i>_<i>fs</i> is greater than <i>P</i>_<i>th</i>.

The percolation threshold, Pth, was calculated from Eq 2 for nm = 1 and At = 7.5. The maximum Hamming distances, nmax, from wildtype sequences where Pfs > Pth were determined from experimental data. Data for β-lactamase comes from Bershtein et al. (2006), for GFP from Sarkisyan et al. (2016), and for HisA from Lundin et al. (2018). The maximum Hamming distances were converted to sequence identities (SI) using Eq 4. The region where Pfs > Pth for all the proteins is where their SI with a wildtype sequence is greater than approximately 95%.