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Fig 1.

Schematic illustration of the WaterDock 2.0 bridging water prediction pipeline.

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Table 1.

The H-bond saturation limit enforced on the various functional groups implemented in the WaterDock 2.0 pipeline.

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Table 2.

The dataset used to validate the ligand-directed Waterdock 2.0 algorithm.

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Fig 2.

The MD (A-E) and modelled (F-J) hydration structure of five polar functional groups. (A, F) carbonyl, (B, G) carboxyl, (C, H) ether, (D, I) phosphoryl, (E, J) imine.

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Fig 3.

The location of water-sites around different amine groups as produced in MD.

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Fig 4.

(A) The distribution of hydration sites around the hydroxyl functional group from MD simulation. (B) The modelled hydration structure of the hydroxyl functional group.

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Fig 5.

Scatter plot showing the water-site’s Vina docking score against the distance to the nearest crystallographic water on application of the WaterDock 2.0 pipeline to the Astex Diverse Set.

The 2.0 Å distance cut-off is plotted as a vertical dotted line and the Vina cut-off score of -0.55 kcal/mol is plotted as a horizontal dotted line. The lower left quadrant thus signifies crystallographic waters molecules correctly identified within the training set.

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Fig 6.

The location of the crystallographic waters from two structures of PIM-1 with PDB accession codes 1XWS and 2BIK, where the crystallographic waters from the two structures are shown in red/blue and the predicted waters from the two runs are shown in green/yellow, respectively.

A false-positive result arises from two sites (green) predicted adjacent to the same crystallographic water (red/blue).

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Table 3.

The results of the validation dataset of eleven protein holo-structures.

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Table 4.

The results of the OppA dataset of structures used to allow comparison of new prediction protocol to AcquaAlta and the original WaterDock methodologies.

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Fig 7.

Snapshots of the PyMOL plugins developed for WaterDock pipelines.

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