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Placement of Water Molecules in Protein Structures: From Large-Scale Evaluations to Single-Case Examples

Cite this: J. Chem. Inf. Model. 2018, 58, 8, 1625–1637
Publication Date (Web):July 23, 2018
Copyright © 2018 American Chemical Society

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    Abstract Image

    Water molecules are of great importance for the correct representation of ligand binding interactions. Throughout the last years, water molecules and their integration into drug design strategies have received increasing attention. Nowadays a variety of tools are available to place and score water molecules. However, the most frequently applied software solutions require substantial computational resources. In addition, none of the existing methods has been rigorously evaluated on the basis of a large number of diverse protein complexes. Therefore, we present a novel method for placing water molecules, called WarPP, based on interaction geometries previously derived from protein crystal structures. Using a large, previously compiled, high-quality validation set of almost 1500 protein–ligand complexes containing almost 20 000 crystallographically observed water molecules in their active sites, we validated our placement strategy. We correctly placed 80% of the water molecules within 1.0 Å of a crystallographically observed one.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jcim.8b00271.

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    Cited By

    This article is cited by 30 publications.

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