Abstract
The control of ion channel permeation requires the modulation of energetic barriers or “gates” within their pores. However, such barriers are often simply identified from the physical dimensions of the pore. Such approaches have worked well in the past, but there is now evidence that the unusual behavior of water within narrow hydrophobic pores can produce an energetic barrier to permeation without requiring steric occlusion of the pathway. Many different ion channels have now been shown to exploit “hydrophobic gating” to regulate ion flow, and it is clear that new tools are required for more accurate functional annotation of the increasing number of ion channel structures becoming available. We have previously shown how molecular dynamics simulations of water can be used as a proxy to predict hydrophobic gates, and we now present a new and highly versatile computational tool, the Channel Annotation Package (CHAP) that implements this methodology.
Highlights
Ion channels form pores that facilitate the selective movement of ions across lipid bilayers
We have previously shown how molecular dynamics simulations of water can be used as a proxy to predict hydrophobic gates, and we present a new and highly versatile computational tool, the Channel Annotation Package (CHAP) that implements this methodology
We present a versatile computational tool for the functional annotation of ion channel structures: the Channel Annotation Package, CHAP
Summary
Ion channels form pores that facilitate the selective movement of ions across lipid bilayers. We have previously shown how molecular dynamics simulations of water can be used as a proxy to predict hydrophobic gates, and we present a new and highly versatile computational tool, the Channel Annotation Package (CHAP) that implements this methodology. We have shown how molecular dynamics (MD) simulations of water behavior within these nanoscale structures can be used to aid the functional annotation of different pentameric ligandgated ion channels (the 5-HT3 and glycine receptors) and demonstrated the existence of hydrophobic gates within these particular structural conformations [22].
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