Water Transport in Aquaporins: Osmotic Permeability Matrix Analysis of Molecular Dynamics Simulations

¹ Yokohama City University

^* To whom correspondence should be addressed. E-mail: ike{at}tsurumi.yokohama-cu.ac.jp.

Submitted on November 17, 2006
Revised on February 6, 2007
Accepted on 23 February 2007

	Abstract

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 (NPA) 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.

Key Words: NPA motif, ar/R region, linear response theory, membrane protein, single-file permeation, water channel