Using the statistical profile, we identified 9 promising designs in the first round for further laboratory experiments to gain deeper insight into the statistical indicators. These designs exhibited a wide range of sequence variability, ranging from 45 substitutions and no insertions or deletions (indels) to 138 substitutions and 109 indels (Table ) (AncDhaA1-9). The substitutions and indels, with deletions in most cases, covered the entire protein structure. In the second round, we focused on the more conserved variants (ancestors 5, 7, and 8; AncDhaA10-12 for reference in experiments) with 7 to 34 substitutions without indels. Altogether, 12 designs were selected for laboratory expression and biophysical characterization from Model 1.