Dynamic and energetic mechanisms for the distinct permeation rate in AQP1 and AQP0.

Despite sharing overall sequence and structural similarities, water channel aquaporin 0 (AQP0) transports water more slowly than other aquaporins. Using molecular dynamics simulations of AQP0 and AQP1, we find that there is a sudden decrease in the distribution profile of water density along the pore of AQP0 in the region of residue Tyr23, which significantly disrupts the single file water chain by forming hydrogen bond with permeating water molecules. Comparisons of free-energy and interaction-energy profiles for water conduction between AQP0 and AQP1 indicate that this interruption of the water chain causes a huge energy barrier opposing water translocation through AQP0. We further show that a mutation of Tyr23 to phenylalanine leads to a 2- to 4-fold enhancement in water permeability of AQP0, from (0.5+/-0.2) x 10(-14) cm(3)s(-1) to (1.9+/-0.6) x 10(-14) cm(3)s(-1). Therefore, Tyr23 is a dominate factor leading to the low water permeability in AQP0. Copyright 2009 Elsevier B.V. All rights reserved.