Fig. 1.

(A) A schematic of the ligand (blue sphere), explicit water, and the pocket of a concave wall. (B) In 1s-dry, the VISM surface (blue line) is a single surface enclosing all of the wall atoms and also the ligand atom and hence a dry state of the pocket. (C) In 2s-dry, the VISM surface has 2 disjoint components, 1 enclosing all of the wall atoms with a dry pocket and 1 enclosing the ligand. (D) In 2s-wet, the VISM surface has 2 components, tightly wrapping up the wall and ligand, respectively, with no space for water and hence a wet pocket.