Molecular dynamics free energy calculations highlighting the role of F357 in the function of the CLC-ec1 Cl-/H+ antiporter

Figure 2:•2D PMF calculations describing the permeation of two Cl- ions in the pore of the CLC-ec1 Cl-/H+ antiporter, with F357 side chain restrained to either of two rotamers, or without any restraint.•1D PMF calculations describing the side chain rotameric transition of residue F357 in the CLC-ec1 Cl-/H+ antiporter. The reaction coordinate is the chi1 angle of F357. PMFs are obtained for different ion occupancy states of sites Scen and Sext (without ion, Sext occupied, Scen occupied, both sites occupied). Each calculation is repeated from two different starting states: chi1 = -70º, or chi1 = -160º. Some of the calculations were also repeated in presence of a crosslink. Figure 3:•Molecular system snapshots extracted from the PMFs of Figure 2A and Figure 3 - Figure supplement 1, in PDB format. •1D PMF calculations describing the binding of a single Cl- ion to the permeation pathway of the CLC-ec1 Cl-/H+ antiporter, when E148 is bound to Scen and is either charged or protonated.The PMF calculations imply umbrella sampling simulations using the CHARMM software version 36 and the CHARMM c36 force field (params.zip).<br>