Structural Analysis
We used Fpocket33to identify the cavities in the available conformers (see Supplementary
Table 2) with known structures of all proteins in the dataset. We
estimated the pKa values of the ionizable residues of these conformers
using PROPKA34,
to identify relevant amino acids for biological function or promiscuous
activity. The residues predicted as being under positive selection were
mapped to the cavities and assigned a pKa when possible. Preparation and
analysis of data were done using custom scripts in the Python
programming language.