Mobility of drugs in equilibrium and metadynamics simulations . (A) Average RMSD of drug for the 20 replicates over 100 ns of unbiased equilibrium simulations compared to 20 walkers over 100 ns of metadynamics simulations – aligned to the Na_v pore domain backbone (residues 236–285, 313–417, 824–945, 1321–1504, and 1641–1780). (B) Average RMSD of drug within each replicates/walkers of unbiased equilibrium simulations compared with metadynamics simulations – fit to the drug. (C) Percentage of frames out of the metadynamics trajectories in each of the top five clusters.