Fig. 8
Prediction of membrane permeabilities. (A) Potential of mean force (PMF) of permeation of M23, M27, and M10. M23 and M27 are additionally considered in their protonated form (M23_H and M27_H, respectively). As a reaction coordinate, the distance to the center of the DOPC membrane bilayer was used, setting the profile in the water phase to zero. M10 and deprotonated M23 and M27 display favorable free energy in the membrane center, while protonated M23_H and M27_H display a high energy barrier in the membrane center. (B) Calibration curve obtained previously by us20 between the calculated permeabilities obtained from MD simulations and the experimental values obtained from PAMPA experiments from36. Using this calibration curve, M23, M27, and M10 are predicted to be highly permeable (note the overlap between their values), while M23_H and M27_H are predicted to be impermeable or low to medium permeable (Table 2). Peff is the effective permeability, and P0 is the unit factor corresponding to 1 cm sec−1. Shaded areas correspond to the standard deviation obtained by splitting each calculation into ten slices of 5 ns simulation time.
