SIpHAB is a sequence-based tool to engineer pH-sensitive antibody binding. It was developed in 2023 by the National Research Council Canada (NRC) Molecular Modeling Team. It was created by analyzing the results and identifying trends in nearly 3500 antibody-antigen structural complexes, which were subjected to dual-pH, histidine-scanning mutagenesis. Benchmarking SIpHAB on several systems substantiated its utility for proposing promising pH-sensitive mutations and has achieved great success in experimental designs. SIpHAB could be applied to enhance binding under either: 1) acidic tumour microenvironments for greater specificity engineering or 2) physiological pH for improved endosomal recycling. Access to SIpHAB is made freely available for both academic and commercial purposes. If you found the method useful and would like more details, please refer to the paper