Table 2.

Bruton’s Tyrosine Kinase (BTK) structures [29–32]

Compound	PDB code [3]	pIC50 [13]	Ligand PIE (kcal/mol)	Water network PIE (kcal/mol)	Water PIE median
6	6AUB	7.92	− 149.0	− 263.3	− 35.9
7	6BIK	8.19	− 184.5	− 174.0	− 30.1
7_A	6BIK	8.19	− 189.2	− 211.6	− 28.6
7_B	6BIK	8.19	− 186.5	− 238.0	− 33.8
8_A	6AUA	8.88	− 169.9	− 277.8	− 36.2
8_B	6AUA	8.88	− 169.0	− 278.8	− 37.2
9	6EP9	6.83	− 150.3	− 214.6	− 37.2
10_A	6BKH	8.88	− 200.1	− 271.2	− 33.9
10_B	6BKH	8.88	− 204.0	− 285.0	− 34.0
11	6BKE	8.34	− 206.3	− 226.3	− 33.5
12	6BLN	8.79	− 164.4	− 305.0	− 40.7
13	6BKW	8.30	− 159.0	− 235.2	− 32.3
14	5VFI	9.04	− 189.9	− 215.5	− 34.7

“Water network PIE” is the total of all the water energies, whereas “Water PIE median” is the median value over the individual water molecules. Median was used as it gives a more appropriate idea of the data distribution. The water molecule #6 in the 6BIK complex has been either removed (compound 7) or represented in two different positions (compounds 7A and 7B). In complex 6AUA, compound 8 is reported in two possible conformations (compounds 8A and 8B). In complex 6BKH, Ser538 can adopt two possible side chain conformations (compounds 10A and 10B, Fig. SI3)