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

TLDR

AQP1 and GlpF function as two‑stage filters, with NPA motifs defining selectivity and an aromatic/arginine region acting as a proton filter. The study performs real‑time molecular dynamics simulations to generate time‑resolved, atomic‑resolution models of water permeation through AQP1 and GlpF. Hydrophobic barriers near the NPA motifs limit water flow; AQP1 requires dipole rotation for selectivity, while GlpF uses glycerol‑induced fit gating to favor glycerol over water.

Abstract

“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.