WATER: WHERE IT MATTERS, WHEN IT MATTERS
All protein-ligand binding interactions occur in an aqueous environment, therefore predicting the effects of solvent molecules within the binding site is a necessary step in understanding binding affinity. However, the interactions of protein and ligand together with water molecules can have complex and non-obvious effects, which can complicate and obfuscate a lead-optimization campaign.
SZMAP is OpenEye’s application to help modelers and medicinal chemists understand the role of water in molecular interactions such as ligand binding. Using water as a lens, SZMAP can provide the user with insight on critical features of a binding site, predict where and how neighboring waters can influence binding of a ligand, or generate ligand modification hypotheses designed to better exploit specific regions on a binding site. The semi-continuum [1, 2] approach used in SZMAP combines one explicit water molecule with robust continuum solvent methods , classical statistical mechanics, and thorough sampling plus the ability to analyze specific water orientations.