WaterMap Overview
In the context of drug design, it can be useful to exploit the displacement of unstable water molecules in the active site of a drug target. Unstable water molecules are usually found in hydrophobic regions, where the waters tend to not have competitive entropy or hydrogen bonding compared to bulk water. Displacement of such waters by the ligand results in significant gains in free energy.
WaterMap is a tool that identifies unstable water molecules on the basis of enthalpies and entropies generated from a Desmond molecular dynamics simulation. The results are displayed in Maestro as a 3D map of the water sites ("hydration sites"), along with a range of other tools for analyzing the waters and their interactions. The purpose of WaterMap is to provide insight into the properties of the water molecules in a protein binding site, thus enabling the design of optimal ligands based on their ability to differentially displace and retain specific water molecules in the binding site.
The mechanics of running WaterMap and analyzing the results is described in the help topics:
The topics listed below provide some information on the process and the interpretation and analysis of the WaterMap results.