Conserved water molecules in X-ray structures highlight the role of water in intramolecular and intermolecular interactions.

Water molecules immobilized on a protein or DNA surface are known to play an important role in intramolecular and intermolecular interactions. Comparative analysis of related three-dimensional (3D) structures allows to predict the locations of such water molecules on the protein surface. We have developed and implemented the algorithm WLAKE detecting "conserved" water molecules, i.e. those located in almost the same positions in a set of superimposed structures of related proteins or macromolecular complexes. The problem is reduced to finding maximal cliques in a certain graph. Despite exponential algorithm complexity, the program works appropriately fast for dozens of superimposed structures. WLAKE was used to predict functionally significant water molecules in enzyme active sites (transketolases) as well as in intermolecular (ETS-DNA complexes) and intramolecular (thiol-disulfide interchange protein) interactions. The program is available online at http://monkey.belozersky.msu.ru/~evgeniy/wLake/wLake.html.