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Size Selectivity in Ion channels

Size Selectivity in Ion channels. Roland Roth Dirk Gillespie. Model of Size Selectivity. what is the simplest system that shows the effect of size selectivity? mixture of uncharged hard spheres that model e.g. water, Na and K

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Size Selectivity in Ion channels

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  1. Size Selectivity in Ion channels Roland Roth Dirk Gillespie

  2. Model of Size Selectivity • what is the simplest system that shows the effect of size selectivity? • mixture of uncharged hard spheres that model e.g. water, Na and K • selectivity filter: protein confines water and ions by a soft and corrugated wall • effective attraction Uattr of ions into the selectivity filter • effective repulsion Vrep of water from the protein • hard-sphere diameter

  3. Bulk Approach to Size Selectivity • system 1: bath • fixed water concentration: rH20 (55.5 M) • fixed ion concentration: rNa, rK,, ... (100 mM) • system 2: filter • attraction for ions into the filter Uattr > 0 (0...10 kB T) • repulsion for water from the protein: Vrep > 0 (0,1,2,3 kB T) • system 1: bath • fixed water concentration: rH20 (55.5 M) • fixed ion concentration: rNa, rK,, ... (100 mM) water and ion concentrations in lter have to be calculated from (i= Na, K, H20) mH201({ri}) = mH202({ri}) - Vrep mNa,K1({ri}) = mNa,K2({ri}) + Uattr

  4. Ideal Gas Approximation absorbance in the filter: xNa,K = rNa,K2 / rNa,K1 Selectivity: S = xNa / xK if ions are point particles no size selectivity possible

  5. Binary Mixture of Water and one Ion Species • binary mixture of water and Na (100 mM) or water and K (100 mM) • sNa / sK = 0.74 selectivity S absorbance in the filter xNa;K small ion selectivity

  6. Ternary Mixture of Water and two Ion Specii • ternary mixture of water, Na (100 mM) andK (100 mM) absorbance in the filter xNa;K selectivity S • small ion selectivity is enhanced through competition between Na and K • small ion selectivity is highly non-linear

  7. Small Ion Selectivity • mechanism: electrostatic attraction of ions into the selectivity filter and • competition for space • depends on ion concentration (50 mM, 100 mM and 150 mM)

  8. Na and K Density Proles • rNa1 = rK1 = 100 mM ; Rpore = 3.5 A • the pore is soft and corrugated, protein can be penetrated by ions • Vattr =2, 6, 8, 10 kBT K density profiles Na density profiles

  9. Hydrophobic Channels Uattr = 0, Vrep = 0,... ,3 kBT models hydrophobic repulsion of water from the protein consider Na and Cs in the bath; sNa / sCs = 0.59; rNa = rCs = 50 mM selectivity: S = xCs / xNa absorbance in the filter xNa;Cs

  10. Na and Cs Density Proles rNa1 = rCs1 = 50 mM; Rpore = 4.2 A Urep =0, 1, 2, 3 kBT Cs density profiles Na density profiles

  11. Large Ion Selectivity • mechanism: water is repelled from the protein (the pore wall) and largest species lls free space • is (almost) independent of ion concentration • is a surface effect • -> best agreement between DFT and bulk approach for small channels

  12. Mixed Channel hydrophobic repulsion (Vrep = 3kBT) and electrostatic attraction (Uattr) SNa = xNa/xCs and SCs = xCs/xNa absorbance of Na and Cs crossover from large (Uattr small) to small ion selectivity (Uattr large)

  13. Conclusions • simple model allows to understand the mechanism for small and large ion selectivity • selectivity filter provides an environment in which the small size difference of the ions get amplied • entropy of ions is very important • small ion selectivity: electrostatic attraction of ion into the selectivity filter and competition between ions for space (bulk effect) • large ion selectivity: hydrophobic repulsion of water from the protein; large ions fill free space (surface effect) • bulk approach is confirmed by DFT calculations

  14. Outlook • include electrostatics into bulk approach (MSA) • attraction of ions into the channel will be generated by electrostatics • additional species (e.g. Cl-) have to be included • include nite channel geometry in DFT approach • include electrostatics into DFT approach

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