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Content archived on 2024-05-27

Association of Aquaporin Transmembrane Channels and Influence of their Oligomerization State on the Transport Properties

Objective

The goals of this proposal are to (i) determine how does the oligomerization state of aquaporin (AQP) transmembrane channels influence the water transport properties of these channels, and to (ii) understand how aquaporins’ association and transport properties change under different lipid composition conditions. The study will be conducted on the human AQP5 aquaporin, whose atomistic high resolution structure has been recently determined. First we will determine the water transport properties of the wildtype tetrameric AQP5 channels from fully atomistic simulations. Then we will compare our results with the corresponding properties we obtain for a single channel in the same lipid bilayer. Second, we will study the association of AQP5 channels in a lipid bilayer closest to its natural environment by describing both the dynamics and the energetics of such associations. Since these processes occur on a mesoscopic timescale, unattainalble from fully atomistic simulations, we will use a coarse-grained model of the AQP5 porins and its surrounding environment. Third, we will investigate the influence of lipid composition on the association of these aquaporins. Fourth, we will compare transport properties of AQP5 channels in various lipids that were studied at the third point. The simulated systems will use fully atomistic models with initial configurations obtained from the coarse-grained simulations. The techniques used in our research proposal are based on free energy profile calculations using well established methods from steered molecular dynamics, as well as new approaches from Monte Carlo based flat-histogram simulations. Our novel approach for studying aquaporins can help us understand better how their association influences their functionality. Furthermore, the proposed investigating methods can be, in principle, extended to any transmembrane Channel that manifest oligomerization.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2009-IIF
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Funding Scheme

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MC-IIF - International Incoming Fellowships (IIF)

Coordinator

UNIVERSITA DEGLI STUDI DI CAGLIARI
EU contribution
€ 165 958,60
Address
VIA UNIVERSITA 40
09124 CAGLIARI
Italy

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Region
Isole Sardegna Cagliari
Activity type
Higher or Secondary Education Establishments
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Total cost

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