Table 3. Molecular dynamics (MD) simulation systems of vesicular monoamine transporter 2 (VMAT2) in the presence of tetrabenazine (TBZ), their properties and simulation durations.
| System ID | Protonated residues | Bound ligand | Duration (ns) | Waters in binding pocket* | RMSD in VMAT2 Cα-atoms (Å)† | RMSD in TBZ heavy atoms (Å) ‡ |
|---|---|---|---|---|---|---|
| TBZ_1 | E312 and D399 | TBZ | 3×180 | 2.8±1.3 | 2.4±0.3 | 2.7±0.5 |
| TBZ_2 | TBZ+ | 2×100 | 8.1±1.4 | 2.4±0.4 | 5.9±1.4 | |
| TBZ_3 | E312, D399, and D426 | TBZ | 3×100 | 4.6±1.4 | 2.7±0.5 | 3.5±1.3 |
| TBZ_4 | TBZ+ | 2×100 | 14.3±2.4 | 2.3±0.2 | 3.7±0.4 |
*
Number of water molecules within 3.5 Å of TBZ (or TBZ+) averaged over multiple MD snapshots.
†
RMSDs (root-mean-square-deviations) of VMAT2 Cα-atoms from their initial (cryo-EM resolved) positions.
‡
RMSD of the heavy atoms of TBZ from their cryo-EM-resolved positions. All averages and standard deviations were calculated between 50 and 100 ns portion of the MD trajectories.