Extended Data Fig. 4: Validation of ligand binding poses with molecular dynamics simulations.
From: Molecular basis of polyspecific drug and xenobiotic recognition by OCT1 and OCT2
a, Three possible poses for DPH molecule placement based on the cryo-EM reconstruction. b, Final MD frame for 5 replicas of DPH-OCT1CS MD simulations (500 ns) for the three proposed poses, where possibility #1 is more stably bound at the site. c, Two possible poses for S(–)-VPM based on the cryo-EM reconstruction. d, Final MD frame for 5 replicas of VPM-OCT1CS MD simulations (500 ns), for the two proposed poses, where possibility #2 is more stable (r.m.s.d. – root mean square deviation from starting pose). e, Zoom-in view of the cryo-EM map and model of the VPM chiral center. f, Inter-atomic distances between the ionizable nitrogen of VPM or DPH and acidic residues (D474 or E386) during the MD-simulations of drug-bound OCT1CS (scatter plot showing individual values extracted per MD frame, compiled from all 5 replicas per condition, with the black line representing the mean).
