Incorporating structural details of charged residues into coarse-grained models of ion channels improves the prediction of ion selectivity and binding sites.
Animal study results warrant no clinical changes to ion channel therapies; leaves open in vivo validation of modeled selectivity.
The simplified coarse grained models of selectivity of Nonner and co-workers predict ion selectivity for a variety of different ion channels. The model includes the charged atoms of the channel's charged residues and permeant ions. However its MC implementation does not take advantage of the increasingly large body of structural information available. Here, we introduce the location of the channel's charged residues into the model's Hamiltonian. In the DEKA Na(+) channel, this allows us to correlate the lysine's topological location directly with the predicted selectivity. In the NanC channel, from Escherichia coli , the dramatic variation in the resulting ion population predicts novel selectivity regions and binding sites that can be directly correlated with structural information. These results have well-defined thermodynamic properties that are significantly modified by structural detail allowing new insights with molecular detail.
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Finnerty et al. (2012) studied this question.
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