This Zenodo record is a permanently preserved version of a comment on a PREreview. You can view the complete PREreview and comments at https://prereview.org/reviews/14480475. We highly appreciate this PREreview and sincerely thank the authors for their kind words about the manuscript and want to emphasize our appreciation for the thorough summary provided. In regard to their comments, we want to emphasize that: 1. The revised version of the manuscript now holds detailed activity data for variants of the most active designs, addressing the question of individual contributions to catalysis from the scaffolded active site tetrad. The new data shows that the individual residues participate in catalysis, yet to different degrees when compared to the evolved variant RA95.5-8f. 2. The background activities most likely originate from a high imidazole concentration in the screening buffer – 96 well based screens were performed with affinity pure protein in elution buffer containing 250mM imidazole. 3. Scaffolding success with larger fragments was an empirical observation during the course of the project. 4. We expanded the section about design selection and provide detailed data for what the structural quality filters are. We implemented the RiffDiff pipeline using a python package that manages protein design tools on SLURM-based computing clusters. We added installation and usage instructions to the implementation which can be accessed here: https://github.com/mabr3112/riff_diff_protflow. The initial code for RiffDiff was written in an early, (local) version of this package and can be viewed here: https://github.com/mabr3112/riff_diff_original. The corresponding design models and data files have been uploaded to Zenodo (https://zenodo.org/records/15494858) Competing interests The author of this comment declares that they have no competing interests.