In round 3, the proposed mutations by VAE were also curated manually (see Section 2 Manual curation of designs in round 3 of SI for more detail). The visual inspection of the modeled AlphaFold variants was performed by Pymol , and the MutCompute web server was used to calculate the score per residue as the log-likelihood ratio of the substitution residue to the original residue type. Thus, a positive score indicates that MutCompute assesses the substituted residue as more likely to occur in the given structural microenvironment than the wild-type residue.