Researchers at St. Jude Children’s Research Hospital have developed ColdBrew, a novel computational algorithm that more accurately models the presence and behavior of water molecules within protein binding sites at physiological temperatures. Existing experimental methods often distort water molecule positions due to cryogenic data collection. ColdBrew leverages extensive protein-water network data to distinguish biologically relevant water molecules from artifacts, enhancing the precision of protein–ligand interaction analysis. This advancement offers a critical tool for drug discovery efforts, enabling finer understanding of binding mechanisms and potentially improving the design of small-molecule therapeutics.