Lynn Kamerlin

Water structure is crucially important to protein function and catalysis and can be conserved throughout related proteins despite differences in sequence. The complex hydrogen-bonding networks formed by water molecules and protein residues have been studied extensively, and graph-theory-based methods have frequently been used to describe these networks. Although there exist a number of tools which can be used to track water positions and networks, corresponding methods for easily analyzing complex water network structure across related proteins are limited. To address this challenge, we present here a new tool, WatCon, an open-source Python package which can be used to analyze water positions and water network structure across protein families using both dynamic and static structural information. Importantly, WatCon can be used to classify conservation of water networks, characterize water networks across structures, and project subsequent results for easy visual interpretation. To illustrate WatCon usage, we provide five example applications illustrating WatCon analyses of static structures, dynamic trajectories, and cross-family analysis. This in turn showcases the utility of WatCon for enhancing our understanding of biochemical systems, predicting water hotspots of potential relevance to protein engineering and predicting pathogenic mutations. WatCon can be downloaded at https://github.com/kamerlinlab/WatCon and is available under the GNU General Public License v3.0.