Stereo views of the WATMD
annotations described in the text, exemplified
for monomeric Mpro (2QCY). In general, solvation shells are loosely
organized into three major strata (demarcated by yellow lines) spanning
between the protein surface and bulk solvent (noting that bulk solvent
per se is omitted from WATMD analyses), as follows: (1) Stratum 1:
ULOVs that are largely or fully devoid of protein H-bond partners,
which reside directly adjacent to nonpolar protein
surface patches, as well as HOVs residing directly adjacent to polar protein surface patches comprised of multiple donors
and/or acceptors; (2) Stratum 2: weaker, partially H-bond depleted
LOVs that bridge between strata 1 and 3; (3) Stratum 3: BLOVs and
H/O-agnostic SBLOVs that bridge between bulk solvent and the outer
reaches of the solvation shell (putatively dominated by lateral water–water
H-bonding). Voxels are denoted by spheres, which are scaled in proportion
to their relative time-averaged H and O occupancies, and color-coded
according to relative preference for O versus H (red and blue, respectively),
or lack thereof (white). (A) Full WATMD grid, viewed toward the protein
surface in the direction of strata 3 to 1. A crystallized Mpro substrate extracted from 2Q6G (magenta) is overlaid on the active site for reference.
Bulk solvent surrounding the solvation shell has been removed, resulting
in an irregular grid boundary. (B) AS of Mpro viewed approximately
parallel to the pocket. Stratum 3 voxels typically consist of BLOVs
(yellow spheres) and SBLOVs (white spheres). (C) Same as B, except
zoomed into stratum 2 voxels, which typically consist of LOVs occupied
by solvation that is weakly H-bonded to a single protein donor or
acceptor (small dark blue spheres). (D) Same as B, except zoomed into
stratum 3 voxels, which typically consist of HOVs occupied by solvation
that is strongly H-bonded to multiple protein donor(s) and/or acceptor(s)
(large spheres) or ULOVs occupied by solvation that is largely or
fully devoid of H-bonds (dot-sized spheres). UHOVs corresponding to
trapped water within buried channels/cavities are not shown.