Scientists at St. Jude Children’s Research Hospital have unveiled ColdBrew, a novel computational algorithm that models protein-bound water molecules under physiological conditions. This method overcomes limitations of cryogenic structure data, which often obscure biologically relevant water positions due to freezing artifacts. ColdBrew analyses extensive water network data to identify tightly bound waters critical for ligand binding, promising to enhance the accuracy of protein-ligand interaction predictions and inform more precise drug design in immunology and oncology.