Setup

1. Setup

3. Crowded Ions Snap Shots of Contents ‘Side Chains’are SpheresFree to move inside channel Radial Crowding is Severe 6Å Parameters are Fixed in all calculations in all solutions for all mutants Boda, Nonner, Valisko, Henderson, Eisenberg & Gillespie

4. Ca and Na Channels

5. AspartateE acid (negative) Lysine K basic (positive)

6. Size SelectivityNa+vs K+inthe DEKA Na ChannelNothing was changed in the model

7. Na+ 2.00 Å K+ Na+ K+ 2.66 Å 6 8 10 Small Channel Diameter Largein Å Boda, et al Size Selectivity (ratio)Depends on Channel Size,not ProteinDielectric Coefficient Selectivity for small ion inDEKA6Å Na Channel

8. DEKANa Channel,6 Å Na+ Occupancy 2.0 Å K+ 2.66Å Occupancy # = Dielectric Coefficient =of Protein Boda, et al Size Selectivityratiodoes not depend on protein dielectricOccupancy # Depends on Protein Dielectric ProteinDielectric ‘Amplifies’ Charge & Electrostatic effects

9. Selectivity is in the Depletion Zonenot the binding site

10. Na+ Na+ Selectivity Filter K+ K+ 0 K+in Depletion Zone Depletion Zone Size Selectivity is in the Depletion Zone Na+vs. K+ Occupancy Channel Protein [NaCl] = 50 mM[KCl] = 50 mM Concentration [Molar] of the DEKA Na Channel, 6 Å Boda, et al

11. Size Selectivity Size Selectivity log C/Cref Selectivity Filter Binding Sites* *Binding Sites are outputs of our model, not structural inputs Selectivity Filter Selectivity Filter Selectivity Filter Selectivity Filter Selectivity Filter Selectivity Filter Lys or K Selectivity Filter D or E BLACK=Depletion=0 [NaCl] = [KCl] = 50 mM Na vs K Size Selectivity is in Depletion Zone Boda, et al

12. Charge Selectivity

13. Na+ 2.0 Å Ca++ 1.98 Å 6 8 10 Small Size  Greater Charge Selectivity Charge SelectivityNa+vs Ca++Depends on Dielectric Dielectric Boundary Force = DBF Small Size andLargeDielectricBoundaryForce DEKA Na Channel, 6 Å Dielectric is a Charge Amplifier 25 15 LargeDielectric Boundary Force Selectivity #Na+/#Ca++ 5 ZeroDielectric Boundary Force Diameter/Å Boda et al