Water transport in aquaporins: osmotic permeability matrix analysis of molecular dynamics simulations.

Single-channel osmotic water permeability (p(f)) is a key quantity for investigating the transport capability of the water channel protein, aquaporin. However, the direct connection between the single scalar quantity p(f) and the channel structure remains unclear. In this study, based on molecular dynamics simulations, we propose a p(f)-matrix method, in which p(f) is decomposed into contributions from each local region of the channel. Diagonal elements of the p(f) matrix are equivalent to the local permeability at each region of the channel, and off-diagonal elements represent correlated motions of water molecules in different regions. Averaging both diagonal and off-diagonal elements of the p(f) matrix recovers p(f) for the entire channel; this implies that correlated motions between distantly-separated water molecules, as well as adjacent water molecules, influence the osmotic permeability. The p(f) matrices from molecular dynamics simulations of five aquaporins (AQP0, AQP1, AQP4, AqpZ, and GlpF) indicated that the reduction in the water correlation across the Asn-Pro-Ala region, and the small local permeability around the ar/R region, characterize the transport efficiency of water. These structural determinants in water permeation were confirmed in molecular dynamics simulations of three mutants of AqpZ, which mimic AQP1.