Table 2.

Summary of the enhanced sampling free energy calculation performed

SystemEnhanced sampling techniqueProduction
NavAb (expanded α-model)—Na+ AWH 200 ns × 6 walkers 
NavAb (expanded π-model)—Na+ AWH 200 ns × 6 walkers 
NavAb (expanded α-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb (resting α-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb (asymmetric α-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb (expanded π-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb expanded π-model (N214L)—Na+ AWH 139 ns × 6 walkers 
NavAb (resting α-model)—lidocaine Well-tempered metadynamics 94 ns × 12 walkers 
NavAb (asymmetric α-model)—lidocaine Well-tempered metadynamics 94 ns × 12 walkers 
NavAb (expanded π-model)—lidocaine Well-tempered metadynamics 140 ns × 16 walkers 
NavAb (expanded α-model)—lidocaine Well-tempered metadynamics 140 ns × 16 walkers 
Pore opening starting from contracted π-model (PDB ID 5VB2 WT) without CTD ABMD 840 ps × 3 replicas 
Pore opening starting from contracted α-model (PDB ID 5VB2) without CTD ABMD 840 ps × 3 replicas 
Pore opening starting from contracted π-model (PDB ID 5VB2 N1211L) without CTD ABMD 840 ps × 3 replicas 
SystemEnhanced sampling techniqueProduction
NavAb (expanded α-model)—Na+ AWH 200 ns × 6 walkers 
NavAb (expanded π-model)—Na+ AWH 200 ns × 6 walkers 
NavAb (expanded α-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb (resting α-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb (asymmetric α-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb (expanded π-model)—lidocaine AWH 200 ns × 6 walkers 
NavAb expanded π-model (N214L)—Na+ AWH 139 ns × 6 walkers 
NavAb (resting α-model)—lidocaine Well-tempered metadynamics 94 ns × 12 walkers 
NavAb (asymmetric α-model)—lidocaine Well-tempered metadynamics 94 ns × 12 walkers 
NavAb (expanded π-model)—lidocaine Well-tempered metadynamics 140 ns × 16 walkers 
NavAb (expanded α-model)—lidocaine Well-tempered metadynamics 140 ns × 16 walkers 
Pore opening starting from contracted π-model (PDB ID 5VB2 WT) without CTD ABMD 840 ps × 3 replicas 
Pore opening starting from contracted α-model (PDB ID 5VB2) without CTD ABMD 840 ps × 3 replicas 
Pore opening starting from contracted π-model (PDB ID 5VB2 N1211L) without CTD ABMD 840 ps × 3 replicas 

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