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Waterdock 2.0: Water placement prediction for Holo-structures with a pymol plugin.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Sridhar, Akshay 
Ross, Gregory A 
Biggin, Philip C 

Abstract

Water is often found to mediate interactions between a ligand and a protein. It can play a significant role in orientating the ligand within a binding pocket and contribute to the free energy of binding. It would thus be extremely useful to be able to accurately predict the position and orientation of water molecules within a binding pocket. Recently, we developed the WaterDock protocol that was able to predict 97% of the water molecules in a test set. However, this approach generated false positives at a rate of over 20% in most cases and whilst this might be acceptable for some applications, in high throughput scenarios this is not desirable. Here we tackle this problem via the inclusion of knowledge regarding the solvation structure of ligand functional groups. We call this new protocol WaterDock2 and demonstrate that this protocol maintains a similar true positive rate to the original implementation but is capable of reducing the false-positive rate by over 50%. To improve the usability of the method, we have also developed a plugin for the popular graphics program PyMOL. The plugin also contains an implementation of the original WaterDock.

Description

Keywords

Binding Sites, Ligands, Protein Binding, Protein Conformation, Proteins, Software, Water

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

12

Publisher

PLOS
Sponsorship
GAR is supported by the Memorial Sloan Kettering Cancer Center, NIH grant P30 CA008748.