Table 2. Sub-pocket-wise water thermodynamics for holo simulations: dTS_trans, dTS_orient, H_solv per water.

The rigidity of sub-pocket S1 is reflected in a higher ordering of water molecules. Enthalpic interactions between solvent and solute are very similar within pockets S1, S4, S5, and S6.

	S6	S5	S4	S3	S2	S1
dTStrans [kcal/mol]	0.11	0.36	0.12	-0.001	-0.052	-0.51
dTSorient [kcal/mol]	-0.45	-0.53	-0.91	-0.22	-0.61	-1.38
Hsolv [kcal/mol]	-10.0	-10.4	-9.69	-3.56	-5.30	-10.0