Representative
conformations of the ligand binding pocket of MD
simulations of apo-TNKS2, TNKS2–XAV complex, TNKS2–OLA
complex, and apo-TNKS2-CSol. The conformations (A–H) are labeled
with (A–H). The conformations (A–H) in this figure correspond
to the positions of (A–H) in Figures 3, 5, and S6. The ligand binding pocket is depicted using
molecular surface representations. The hydrophilic and lipophilic
regions are drawn in purple and green, respectively. The bound ligands
(XAV and OLA) are shown using ball-and-stick models. (A) An apo-TNKS2
conformation (23.3 ns). (B–E) Representative conformations
(700.6, 414.5, 580.0, and 549.2 ns, respectively) of the TNKS2–XAV
complex. (F) A TNKS2–OLA complex conformation (60.4 ns). Conformations
(A–D) exhibit the NI-open/AD-closed form. Conformations (E)
and (F) exhibit the NI-open/AD-open form. Conformations (G) and (H)
are representative conformations of apo-TNKS2-CSol (616.3 and 49.6
ns), which exhibit the NI-open/AD-closed and NI-open/AD-open forms,
respectively.