Table 1.
Summary of RAMD simulation details and parameters. All RAMD simulations were carried out with an acceleration of 0.1 kcal/mol Å. Occupancy of the S1 and S2 pockets is noted. In all cases (with the exception of R7 and R8) the force in the RAMD simulations was applied to the substrate found in S1. In R7 and R8, no substrate was docked in S1, and thus the force was applied to amphetamine and cocaine in the S2 pockets.
| Setup | Transporter | S1 | S2 | # of Trajectories | # Extra. Egresses | # Intra. Egresses | # Failed Escapes | Simulation Length Range |
|---|---|---|---|---|---|---|---|---|
| R1 | LeuTAa | Leu | - | 40 | 7 (17.5%) | 31 (77.5%) | 2 (5%) | 0.1 - 0.7 ns |
| R2 | LeuTAa | Leu | Leu | 50 | 0 | 27 (54%) | 23 (46%) | 38 ps - 1 ns |
| R3 | LeuTAa M1 | Leu | - | 49 | 0 | 46 (94%) | 3 (6%) | 23 ps - 0.3 ns |
| R4 | LeuTAa M2 | Leu | - | 50 | 0 | 46 (92%) | 4 (8%) | 28 ps - 0.3 ns |
| R5 | LeuTAa M1 | Leu | Leu | 50 | 0 | 49 (98%) | 1 (2%) | 34 ps - 1 ns |
| R6 | DAT | DA | - | 50 | 18 (36%) | 28 (56%) | 4 (8%) | 0.1 - 0.7 ns |
| R7 | DAT | - | AMA | 50 | 44 (88%) | 3 (6%) | 3 (6%) | 46 ps -1 ns |
| R8 | DAT | - | COC | 50 | 50 (100%) | 0 | 0 | 24 - 31 ps |
| R9 | DAT | DA | DA | 49 | 24 (49%) | 20 (41%) | 5 (10%) | 80 ps - 0.9 ns |
| R10 | DAT | DA | AMA | 50 | 32 (64%) | 10 (20%) | 8 (16%) | 80 ps - 0.7 ns |
| R11 | DAT | DA | COC | 49 | 22 (45%) | 11 (22%) | 16 (33%) | 6 ps - 0.1 ns |