WaterAlignment: Identification of displaced water molecules in molecular docking using Jonker and Volgenant shortest path augmentation for linear assignment

The dynamics of individual water molecules has a strong effect on the energetics of biochemical interactions, such as peptide–protein binding. Existing software are able to predict the location of water molecules at the interface between a macromolecule and a ligand in a single state or at a particular time point. The program described in this article compares explicit solvent molecules from two different states within a given volume of space; for example between a free protein vs. the same protein with a ligand bound. This comparison creates a unique one-to-one matching between waters from the two states utilizing the Jonker and Volgenant algorithm for linear assignment. Matchings are deterministic and minimize the sum of the distance between matched pairs. Explicit solvent ligand docking can utilize this matching to understand how ligand binding affects the energy of interface waters. This algorithm can also be used to compare predicted water molecules to those seen in X-ray crystallography, or to compare two different methods of solvent prediction.