Summary table of equilibrium simulations performed
| System . | Equilibration . | Production . |
|---|---|---|
| NavAb expanded α-model (PDB ID 5VB8) | 30 ns | 185 ns (unrestrained) |
| NavAb expanded α-model I217C (PDB ID 5VB8) | 30 ns | 250 ns (Cα restrained) |
| Expanded π-model | 30 ns | 154 ns (unrestrained) |
| NavAb expanded α-model (PDB ID 5VB8) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded α-model (+750 mV) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded α-model (−750 mV) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded π-model (PDB ID 5VB8) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded π-model (PDB ID 5VB8) | 30 ns | 154 ns (unrestrained) |
| NavAb expanded α-model + lidocaine | 30 ns | 200 ns (Cα restrained) |
| NavAb asymmetric α model + lidocaine | 30 ns | 200 ns (unrestrained) |
| NavAb resting α model + lidocaine | 30 ns | 200 ns (unrestrained) |
| NavAb expanded π-model + lidocaine | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded π-model N1211L | 30 ns | 200 ns (Cα restrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—300 K—Charmm36m | 36 ns | 200 ns (unrestrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—320 K—Charmm36m | 36 ns | 308 ns (unrestrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—360 K—Charmm36m | 36 ns | 309 ns (unrestrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—400 K—Charmm36m | 36 ns | 215 ns, 223 ns, 232 ns (unrestrained) |
| NavAb contracted π-model (PDB ID 5VB2) with CTD | 36 ns | 200 ns (unrestrained) |
| NavAb contracted π-model (PDB ID 5VB2 WT) without CTD | 36 ns | Equilibrated structure used for ABMD simulation × 3 |
| NavAb contracted α-model (PDB ID 5VB2) without CTD | 36 ns | Equilibrated structure used for ABMD simulation × 3 |
| NavAb contracted α-model (PDB ID 5VB2 N1211L) without CTD | 36 ns | Equilibrated structure used for ABMD simulation × 3 |
| System . | Equilibration . | Production . |
|---|---|---|
| NavAb expanded α-model (PDB ID 5VB8) | 30 ns | 185 ns (unrestrained) |
| NavAb expanded α-model I217C (PDB ID 5VB8) | 30 ns | 250 ns (Cα restrained) |
| Expanded π-model | 30 ns | 154 ns (unrestrained) |
| NavAb expanded α-model (PDB ID 5VB8) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded α-model (+750 mV) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded α-model (−750 mV) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded π-model (PDB ID 5VB8) | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded π-model (PDB ID 5VB8) | 30 ns | 154 ns (unrestrained) |
| NavAb expanded α-model + lidocaine | 30 ns | 200 ns (Cα restrained) |
| NavAb asymmetric α model + lidocaine | 30 ns | 200 ns (unrestrained) |
| NavAb resting α model + lidocaine | 30 ns | 200 ns (unrestrained) |
| NavAb expanded π-model + lidocaine | 30 ns | 200 ns (Cα restrained) |
| NavAb expanded π-model N1211L | 30 ns | 200 ns (Cα restrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—300 K—Charmm36m | 36 ns | 200 ns (unrestrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—320 K—Charmm36m | 36 ns | 308 ns (unrestrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—360 K—Charmm36m | 36 ns | 309 ns (unrestrained) |
| NavAb contracted α-model (PDB ID 5VB2) with CTD—400 K—Charmm36m | 36 ns | 215 ns, 223 ns, 232 ns (unrestrained) |
| NavAb contracted π-model (PDB ID 5VB2) with CTD | 36 ns | 200 ns (unrestrained) |
| NavAb contracted π-model (PDB ID 5VB2 WT) without CTD | 36 ns | Equilibrated structure used for ABMD simulation × 3 |
| NavAb contracted α-model (PDB ID 5VB2) without CTD | 36 ns | Equilibrated structure used for ABMD simulation × 3 |
| NavAb contracted α-model (PDB ID 5VB2 N1211L) without CTD | 36 ns | Equilibrated structure used for ABMD simulation × 3 |
Restrained production simulations (where indicated) were used to prevent pore collapse in the absence of CTD. Ion permeation and drug permeation free energy calculations.