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Aquaporins pp 57-76 | Cite as

Dynamics and Energetics of Permeation Through Aquaporins. What Do We Learn from Molecular Dynamics Simulations?

  • Jochen S. Hub
  • Helmut Grubmüller
  • Bert L. de Groot
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 190)

Aquaporins (AQPs) are a family of integral membrane proteins, which facilitate the rapid and yet highly selective flux of water and other small solutes across biological membranes. Molecular dynamics (MD) simulations contributed substantially to the understanding of the molecular mechanisms that underlie this remarkable efficiency and selectivity of aquaporin channels. This chapter reviews the current state of MD simulations of aquaporins and related aquaglyceroporins as well as the insights these simulations have provided. The mechanism of water permeation through AQPs and methods to determine channel permeabilities from simulations are described. Protons are strictly excluded from AQPs by a large electrostatic barrier and not by an interruption of the Grotthuss mechanism inside the pore. Both the protein's electric field and desolvation effects contribute to this barrier. Permeation of apolar gas molecules such as CO2 through AQPs is accompanied by a large energetic barrier and thus can only be expected in membranes with a low intrinsic gas permeability. Additionally, the insights from simulations into the mechanism of glycerol permeation through the glycerol facilitator GlpF from E. coli are summarized. Finally, MD simulations are discussed that revealed that the aro-matic/arginine constriction region is generally the filter for uncharged solutes, and that AQP selectivity is controlled by a hydrophobic effect and steric restraints.

Keywords

Water Permeation Uncharged Solute Grotthuss Mechanism Desolvation Effect Hydrogen Bond Partner 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Jochen S. Hub
    • 1
  • Helmut Grubmüller
    • 2
  • Bert L. de Groot
    • 1
  1. 1.Computational Biomolecular Dynamics GroupMax-Planck-Institute for Biophysical ChemistryGöttingenGermany
  2. 2.Department of Theoretical and Computational BiophysicsMax-Planck-Institute for Biophysical ChemistryGöttingenGermany

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