The resulting converged free energy profile G is symmetric with respect to the central plane of the membrane, as expected. It increases from the water phase into the hydrophobic core. The resulting activation free energy barrier. This result may be used to calculate the permeability coefficient, which can be compared with the related experimental quantity. The latter has been measured for b-lactam antibiotics across the bacterial membrane and for boric acids across membrane vesicles. We calculated a value of permeability coefficient ranging from 761029 to 8610212 cm/s. The upper value is in the range of experimental values measured with other systems. Using the Arrhenius formula the barrier may also be associated to a PF-4217903 moa timescale ranging from 1023 s to 3 s. Further experiments are required to test the validity of these predictions. The inspection of the permeation mechanism clearly shows that the B-2 moiety H-bonds to one or more water molecules upon leaving the membrane surface: this is clearly shown by the B2 �Cwater coordination numbers as well as visual inspection of representative metadynamics snapshots. The water molecule is connected to other water molecules in a chain like monomolecular channel. At the transition state, the channel connecting BZB with side A starts to break. Drug permeation causes some rearrangement of the membrane surface. The calculated dipole of BZB is 2.85 Debye. It points towards the B-2 group. The H angle between m and the z direction is as small as 35u inside the membrane where the compound tends to align with the lipids tails. This has been observed for similar drugs. Instead H increases up to 60u, when the drug is in contact with the solvent, possibly because of the formation of H-bonds with the charged groups of the phospholipids as well as with water molecules. This is the molecular rationale for the observed behaviour that polar molecules tend to decrease the dipole potential of the membrane being absorbed in a direction that is perpendicular to the existing membrane dipole. In this work, we have reported a combined experimental and computational study on the permeation of BZB through model membranes. Our experiments BKM120 PI3K inhibitor establish that BZB passes through the membrane both in charged and neutral form, as it was proposed in our previous work, where the neutral form, more lipophilic, is known to move faster; the translocation of neutral BZB occurs via permeation though the membrane and is not assisted by porins. In our model the neutral BZB translocates assisted by a water channel bound to the boronic group. The neutral form is present in much smaller concentration than the negative one at pH 7.35. For comparison, the positively charged BZD compound with lower pKa, displays higher antibacterial activity and is shown to cross the membrane through porin channels. In this work, we have obtained more insights on the structural and energetic features associated with the permeation of BZB in the neutral form through the membrane via molecular dynamics simulations. Our calculations provide a permeability coefficient similar to that found for some antibiotics and characterized by a translocation time ranging from 1023 s to 3 s; they suggest that the hydrophilic part of the molecule is partially hydrated during the whole permeation process. In particular, a monomolecular water channel assists translocation, the BZB dipole tends to align to the lipid tails inside the membrane and, as a consequence, contribute to the overall SCC transient signal observed in our experiments.