European Biophysics Journal

, 38:347

Ion channel gates: comparative analysis of energy barriers

  • Kaihsu Tai
  • Shozeb Haider
  • Alessandro Grottesi
  • Mark S. P. Sansom
Original Paper

Abstract

The energetic profile of an ion translated along the axis of an ion channel should reveal whether the structure corresponds to a functionally open or closed state of the channel. In this study, we explore the combined use of Poisson–Boltzmann electrostatic calculations and evaluation of van der Waals interactions between ion and pore to provide an initial appraisal of the gating state of a channel. This approach is exemplified by its application to the bacterial inward rectifier potassium channel KirBac3.1, where it reveals the closed gate to be formed by a ring of leucine (L124) side chains. We have extended this analysis to a comparative survey of gating profiles, including model hydrophobic nanopores, the nicotinic acetylcholine receptor, and a number of potassium channel structures and models. This enables us to identify three gating regimes, and to show the limitation of this computationally inexpensive method. For a (closed) gate radius of 0.4 nm < R < 0.8 nm, a hydrophobic gate may be present. For a gate radius of 0.2 nm < R < 0.4 nm, both electrostatic and van der Waals interactions will contribute to the barrier height. Below R = 0.2 nm, repulsive van der Waals interactions are likely to dominate, resulting in a sterically occluded gate. In general, the method is more useful when the channel is wider; for narrower channels, the flexibility of the protein may allow otherwise-unsurmountable energetic barriers to be overcome.

Keywords

Ion channel Gate Electrostatics Model Simulation 

Abbreviations

MscL

Large-conductance mechanosensitive channel

MscS

Small-conductance mechanosensitive channel

nAChR

Nicotinic acetylcholine receptor

PB

Poisson–Boltzmann

PMF

Potential of mean force

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Copyright information

© European Biophysical Societies' Association 2008

Authors and Affiliations

  • Kaihsu Tai
    • 1
  • Shozeb Haider
    • 1
    • 2
  • Alessandro Grottesi
    • 1
    • 3
  • Mark S. P. Sansom
    • 1
  1. 1.Department of BiochemistryUniversity of OxfordOxfordUK
  2. 2.Cancer Research UK Biomolecular Structure Group, Department of Pharmaceutical and Biological Chemistry, The School of PharmacyUniversity of LondonLondonUK
  3. 3.CASPUR Consorzio Interuniversitario per le Applicazioni del Supercalcolo per Università e RicercaRomeItaly

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