The data collection is optimized to preserve catalytic activities. The first step of our pipeline is to construct an MSA. Instead of using Pfam alignments as in , we narrowed the search of relevant sequences to those likely to preserve the dehalogenation activity. Pfam MSAs are sometimes too broad, introducing large-gapped regions and making it difficult to design proteins with desired functions . To overcome this challenge, we used the EnzymeMiner web tool , which generates alignments specifically selected for function and catalytic site similarity (Fig. ).