Ion exclusion mechanism in aquaporin at an atomistic level

Although the mechanism of proton exclusion in aquaporin is investigated by many researchers, the detailed molecular mechanism for ion exclusion in aquaporin is still not completely understood. In the present work, a detailed mechanism for ion exclusion in aquaporin-1 (AQP1) at an atomistic level is investigated by calculating the free energy for transport of ions in AQP1 using an atomistic molecular dynamics simulation. For this purpose, sodium and chloride ions are chosen as representatives for nonprotonic ions. The simulation shows that the free energy barrier showing its maximum is located at the NPA region for sodium ion while it is located at both the front and the rear for chloride ion and that the barrier height is 18 and 9 kcal/mol, respectively, indicating that the ions are not able to pass through aquaporin. Analysis of the pair interaction energy between the permeating ion and its environment reveals that sodium ion is excluded by the positive charge generated by two α-helical macro-dipoles, while chloride ion is expelled by carbonyl oxygen atoms protruding from pore-making residues before it reaches the NPA motif. It is also found that the number of water molecules hydrating the ions is reduced as the ions enter the pore, implying that the energetic cost for detaching water molecules from a permeating ion also contributes to the free energy barriers of ion transport in AQP1.