Table 1. Summary of Results from Clustering of MD Snapshots of the Binding Site Solvent Networks for 13 Protein–Ligand Complexes in the Presence and Absence of Ligands.
| crystal
waters |
hydration sites with
ligand |
||||
|---|---|---|---|---|---|
| protein | PDB codea | binding siteb | bridgingc | presentd | absente |
| acetylcholinesterase | 1e66 (1ea5) | 5 (5/4) | 2 | 10 | 8 (22) |
| coagulation factor VII | 1w7x (1klj) | 19 (12/10) | 4 | 22 | 16 (34) |
| fatty acid binding protein adipocyte | 2nnq (3q6l) | 7 (7/5) | 2 | 9 | 6 (22) |
| glutamate ionotropic receptor, AMPA subunit 2 | 3kgc (4o3b) | 13 (8/7) | 3 | 13 | 11 (25) |
| heat shock protein 90-alpha | 1uyg (1uyl) | 11 (8/7) | 4 | 14 | 10 (19) |
| tyrosine-protein kinase JAK2 | 3lpb | 9 (6/6) | 3 | 11 | 10 (24) |
| poly[ADP-ribose] polymerase-1 | 3l3m | 4 (4/4) | 2 | 11 | 11 (23)f |
| serine/threonine-protein kinase PLK1 | 2owb | 10 (6/5) | 2 | 8 | 6 (16)f |
| protein-tyrosine phosphatase 1B | 2azr (2cm2) | 2 (2/1) | 2 | 7 | 3 (14) |
| GAR transformylase | 1njs | 12 (10/7) | 3 | 19 | 12 (31)f |
| muscle glycogen phosphorylase | 1c8k | 6 (6/5) | 2 | 11 | 11 (21) |
| thrombin | 1ype (2uuf) | 5 (3/1) | 2 | 11 | 4 (22) |
| trypsin I | 2ayw (1s0q) | 10 (5/3) | 4 | 15 | 9 (24) |
| sum: | 113 (82/65) | 35 | 161 | 117 (297) | |
PDB codes of reference crystal structures of the holo and apo (in parentheses) forms.
Number of waters in the binding site of the crystal structure, i.e. within 4 Å of both the protein and ligand. The number of binding site crystal waters that were reproduced by hydration sites derived from simulations carried out with the ligand present/absent, respectively, is shown in parentheses.
Number of crystal waters that bridge protein–ligand interactions, i.e. within 3.3 Å of a polar atom (N or O) of both the ligand and protein.
Number of hydration sites within 4 Å of the protein and ligand from MD simulations carried out in the presence of the ligand.
Number of hydration sites within 4 Å of the protein and ligand from MD simulations carried out in the absence of the ligand after removing sites that overlap with the ligand. The number of hydration sites prior to removing the hydration sites that overlapped with the ligand is shown in parentheses.
This protein was excluded from the analysis of frequently observed ordered waters (Table S2), which resulted in a total of 227 hydration sites.