CA2 and neoplasm: Two protein–ligand systems were selected for investigation:trypsin with a series of p-substituted benzamidinesand carbonic anhydrase II (CAII) with a series of aromatic sulfonamides.41,42 These systems were chosen based on their reported sensitivity towater network effects,43−45 but in addition to being popular model systems inbiochemical and drug design efforts, both proteins are relevant drugtargets in oncology: trypsin overexpression is connected to colorectalcancer,46 while CAII upregulation is connectedto tumor progression and metastasis.47