AquaBridge: A novel method for systematic search of structural water molecules within the protein active sites.

We have developed a novel method for calculation of the water bridges that can be formed in the active sites of proteins in the absence or in the presence of small-molecule ligands. We tested its efficiency on a representative set of human ATP-binding proteins, and show that the docking accuracy of ligands can be substantially improved when water bridges are included in the modeling of protein-ligand interactions. Our analysis of binding pocket hydration can be a useful addition to the in silico approaches of Drug Design.