Table 5. Molecular dynamics (MD) simulations of vesicular monoamine transporter 2 (VMAT2) in the presence of dopamine and the observed events.
| System # | Protonated residues | Duration(ns) | Waters in binding pocket* | VMAT2 RMSD† fromcryo-EM (Å) | Observed events |
|---|---|---|---|---|---|
| DA_0 | None | 2×100 | 7.7±1.5 | 2.6±0.2 | Salt bridge formation between DA and D399; influx of water into the binding pocket. |
| DA_1 | D399 | 2×100 | 10.5±2.2 | 2.2±0.2 | Salt bridges formation between DA and E312; influx of water into the binding pocket. |
| DA_2 | E312, D399 | 2×100 | 8.8±2.1 | 2.2±0.3 | Fluctuations in DA binding pose while remaining within the binding pocket. Formation of two water wires. |
| DA_3 | E312, D399, D426 | 2×100 | 8.8±2.1 | 2.5±0.2 | Fluctuations in DA binding pose; dislocation of DA from its binding site in one of the two simulations. |
| DA_4 | E312, D399, D426, D33 | 1×100 1×200 |
11.7±2.3 | 2.6±0.3 | Fluctuations in DA binding pose; dislocation and release of DA in the 200 ns run. |
*
Number of water molecules within 3.5 Å of dopamine averaged over MD snapshots recorded in the time interval 50–100 ns.
†
RMSDs (root-mean-square-deviations) in VMAT2 Cα-atoms positions; all averages and standard deviations refer to the portion 50–100 ns of MD simulations.