Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore
Fig 4
Molecular dynamic simulation of DHS passing through the Ec-MscL channel with an EEF of 0.2 volt/Å applied to DHS.
(A) ΔZ is defined as the Z coordinate difference of two geometrical centers of DHS and five K106 LYS residues (monomer 1: K106; monomer 2: K242; monomer 3: K378; monomer 4: K514, and monomer 5: K650) which are K106 in monomer labeling. If DHS is located in or above the plane formed by the five LYS, ΔZ > = 0, otherwise ΔZ < 0. (B) The ΔZ plot of DHS passing through Ec-MscL. Five representative conformations labeled as I, II, III, IV, and V, were selected for structural analysis. (C) The fluctuation of the MM-PB energy of Ec-MscL/DHS along the MD simulation trajectory of the passing-through event. (D) The average shifts along Z-axis of 95 K+ during the MD simulation. The negative displacements imply ions go towards outside of the membrane. (E) Representative conformations of the five stages of DHS passing through the Ec-MscL channel event superposed to the last snapshot of the ligand-free MD simulation. DHS is shown as green balls. The reference structure in blue representation is a closed conformation. All the representative conformations of the five passing-through stages are shown as red ribbons. From Conformations I to V, the C-terminal helixes and TM1 are deformed progressively, while no significant difference is observed for S1 and TM2.