New tool uncovers hidden water patterns in protein structures

Every protein in the body is encased in a water shell that directs protein structure, provides vital stability and steers function. Water molecules represent a powerful foothold in drug binding studies. St. Jude Children's Research Hospital scientists have unveiled a new computational tool called ColdBrew to address this problem. The tool predicts the likelihood of water molecule positions within experimental protein structures, potentially aiding drug discovery efforts. ColdBrew was published in Nature Methods.

Proteins fold precisely according to the repulsion and attraction of their amino acid building blocks to water. Water guides other molecules, including drug molecules, to bind effectively. Structural data about water networks collected at freezing temperatures can carry artifacts. Marcus Fischer, PhD, recognized this as a missed opportunity.

With ColdBrew, Fischer and Justin Seffernick, PhD, developed a tool that predicts water molecule positions and provides clues about how ligands bind to proteins. This is crucial for drug discovery as ligands kick out water from binding sites. ColdBrew calculations have been made publicly available to assist researchers.

The study was supported by grants from the National Institutes of Health and ALSAC.