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Science 14 December 2001:
Vol. 294. no. 5550, pp. 2353 - 2357
DOI: 10.1126/science.1062459
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Reports

Water Permeation Across Biological Membranes: Mechanism and Dynamics of Aquaporin-1 and GlpF

Bert L. de Groot, Helmut Grubmüller*

"Real time" molecular dynamics simulations of water permeation through human aquaporin-1 (AQP1) and the bacterial glycerol facilitator GlpF are presented. We obtained time-resolved, atomic-resolution models of the permeation mechanism across these highly selective membrane channels. Both proteins act as two-stage filters: Conserved fingerprint [asparagine-proline-alanine (NPA)] motifs form a selectivity-determining region; a second (aromatic/arginine) region is proposed to function as a proton filter. Hydrophobic regions near the NPA motifs are rate-limiting water barriers. In AQP1, a fine-tuned water dipole rotation during passage is essential for water selectivity. In GlpF, a glycerol-mediated "induced fit" gating motion is proposed to generate selectivity for glycerol over water.

Theoretical Molecular Biophysics Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
*   To whom correspondence should be addressed. E-mail: hgrubmu{at}gwdg.de

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