1. The Role of Long-Range Forces in Porin Channel Conduction S. Aboud Electrical and Computer Engineering Department, Worcester Polytechnic Institute, Worcester MA 01760 D. Marreiro, M. Saraniti Electrical and Computer Engineering Department, Illinois Institute of technology, Chicago IL 60612 R. Eisenberg Molecular Biophysics Department Rush University, Chicago IL 60616

2. Introduction  Particle-Based Simulation Tool  Brownian Dynamics  Force-Field Scheme  Computational Domain/Results  Electrolyte/Lipid System  OmpF Porin Channel  Conclusion/Future Work Motivation: Examine the influence of a fully self-consistent force field scheme on conduction in ion channels.

3. Particle-Based Brownian Dynamics Simulation end simulation time ? NO YES calculate charge calculate averages particle dynamics end initialization field equation Langevin Equation Gaussian white noise Friction coefficient 3 rd order integration scheme: 20 fs timestep

4. Poisson P 3 M Force Field Scheme TSC Interaction between cation and anion in a 0.5 M KCl solution.

5. Electrolyte Solution Dirichlet: Neumann: RDF Radial distribution function Thermodynamic Properties Boundary Conditions

6. OmpF Porin Channel TYR40 ARG42 ARG82 ARG132 TYR102 TYR106 ASP113 GLU117 Atomic structure: 2OMF.pdb, S. W. Cowen et al. Nature 358 (1992). Charge distribution: GROMACS pH=7; total charge: -30e

7. Lipid Membrane/Channel System     

8. Potential Energy Profile I: P 3 M vs PP PP P3MP3M 9 nm 10 nm 11 nm V A =0.0 V cation (K + )

9. Potential Energy Profile II: cation vs anion anion (Cl-) cation (K+) 9 nm 10 nm 11 nm V A =0.0 VP3MP3M

10. Potential Energy Profile III: cation in pore no cation 9 nm 10 nm 11 nm V A =0.0 V P3MP3M anion (Cl + ) cation in pore I

11. cation in pore 1 Minimum potential energy pathway pore 2 pore 3

12. Channel flux correlation correlation coefficient  Ion-ion pairing within a single pore is observed in BD/MD simulations (W. Im et al. J. Mol. Biol. v322 2002). V A =1.0 V 100 mM KCl

13. Channel Flexibility ARG GLU ASP  Bending  Rotation -1e +1e -1e

14. Conclusion  The long-range interactions are apparent at zero bias.  The presence of ions in one pore can change the electrostatic profile seen by charges in the other pores.  The number of positive and negative charges in the 3 pores shows evidence of correlation.  Different charge distribution scheme: e.g. CHARM  Different dielectric constants  Current-voltage characteristics  Flexible channel structure For the specific charge distribution and dielectric constants: Future Work