Ion channel gating: insights via molecular simulations.
Ion channels are gated, i.e. they can switch conformation between a closed and an open state. Molecular dynamics simulations may be used to study the conformational dynamics of ion channels and of simple channel models. Simulations on model nanopores reveal that a narrow (<4 A) hydrophobic region can form a functionally closed gate in the channel and can be opened by either a small (approximately 1 A) increase in pore radius or an increase in polarity. Modelling and simulation studies confirm the importance of hydrophobic gating in K channels, and support a model in which hinge-bending of the pore-lining M2 (or S6 in Kv channels) helices underlies channel gating. Simulations of a simple outer membrane protein, OmpA, indicate that a gate may also be formed by interactions of charged side chains within a pore, as is also the case in ClC channels.
Beckstein
Oliver
O
Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Biggin
Philip C
PC
Bond
Peter
P
Bright
Joanne N
JN
Domene
Carmen
C
Grottesi
Alessandro
A
Holyoake
John
J
Sansom
Mark S P
MS
D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013816:Thermodynamics
D001425:Bacterial Outer Membrane Proteins; D007473:Ion Channels; D015221:Potassium Channels; C078167:OMPA outer membrane proteins