Scientists at St. Jude Children’s Research Hospital developed ColdBrew, an innovative computational algorithm that accurately models water molecule positioning in protein binding sites at physiological temperatures. Traditional cryogenic structural methods distort water networks critical for protein-ligand interactions, impacting drug design precision. ColdBrew leverages water network data to distinguish biologically relevant waters, refining insights into molecular binding and advancing targeted drug development. This technology represents a significant step toward overcoming longstanding challenges in understanding hydration effects integral to accurate drug discovery workflows.