Emerging Concepts in Ion Channel Biophysics

Emerging Concepts in Ion Channel Biophysics

Poster Abstracts

7-POS Board 7 Statistical Kinetic Theory Insights into Selective Conduction in Biological Ion Channels William Gibby 1 , Dmitry G. Luchinsky 1,2 , Miraslau L. Barabash 1 , Olena A. Fedorenko 3 , Stephen K. Roberts 3 , Peter McClintock 1 . 1 Lancaster University, Department of Physics, Lancaster, United Kingdom, 2 SGT Inc, Greenbelt, MD, USA, 3 Lancaster University, Division of Biomedical and Life Sciences, Lancaster, United Kingdom. Biological ion channels are capable of fast conduction at near to the diffusion rate, coexisting alongside highly selective conduction. In this study we investigate selectivity between ions of the same valence, in the highly charged narrow region of the pore that forms the selectivity filter (SF). Selectivity is due to the mismatch of species excess chemical potentials, with a variety of contributions including hydration, surface tension, bonding and more [1]. The SF has a constrained geometry producing a set of quantised occupancy states due to interaction with the fixed charge associated with the amino acid residues forming the SF. We have previously demonstrated in a simple kinetic and statistical model that conduction and selectivity of channels can be described by detailed analysis of the species excess chemical potentials [2,3]. This work is extended by introducing distinguishable binding sites taking into account direct site-dependent interactions. This increases our state space and allows for the full transition pathway to be investigated, alongside the effect of SF structure mutations on the permeation process. Specifically, we have compared theoretical predictions with experimental recordings of Na + and K + conduction and selectivity in NaChBac (and its mutants), to gain physical insight into selectivity and estimate the values of the excess chemical potentials [4]. We expect the results to be applicable beyond biological systems to include artificial nanopores. The research was supported by the Engineering and Physical Sciences Research Council UK (grant No. EP/M015831/1). [1] Roux, B., et al., Quart. Rev. Biophys. 37.01 (2004).

[2] Gibby, W. A. T., et al., arXiv preprint arXiv:1704.03267 (2017). [3] Luchinsky, D. G., et al., arXiv preprint arXiv:1604.05758 (2016). [4] Kaufman, I. Kh., et al., arXiv preprint arXiv:1612.02744 (2016).

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