Boltzmann Transport Monte Carlo Code - BioMOCA NIH Nanomedicine Center for Design of Biomimetic Nanoconductors Network for Computational Nanotechnology (NCN) & NanoHUB Reza Toghraee and Umberto Ravaioli Beckman Institute & ECE Department University of Illinois at Urban-Champaign

National Center for Design of Biomimetic Nanoconductors R eza T oghraee BioMOCA code Adaptation of the Monte Carlo approach used for solid- state device simulation. Germane to Brownian Dynamics with implicit water description, but interaction between ions and water is resolved using a scattering process. BioMOCA code - developed by Trudy van der Straaten, Gulzar Kathawala, Reza Toghraee, and Umberto Ravaioli at the University of Illinois. Development funded by DARPA and NSF Network for Computational Nanotechnology.

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Ion Channels Biological membranes are made out of lipids to protect the valuable interior contents of the cell Membrane proteins are embedded in the membrane bilayer lipid Ion channels answer the need for transport system Highly specific filters For instance, ion channels play a key role in heart pulsing, neuron and muscle cells, toxins, and are related to many diseases

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Motivations Engineers trying to model channels similar to devices In particular we are interested in bio-inspired structures, to realize –sensors –artificial organs –nano batteries –etc…

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Computational Goals and Methods Quantum Chemistry –Very few particles Molecular Dynamics –Extremely costly –Limited time intervals Ion traversal is a rare lucky event A large number of ion crossings must be detected Monte Carlo / Brownian Dynamics –BioMOCA is based on Transport Mante Carlo Continuum Models

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Transport Monte Carlo Particle Simulations 3D particle trajectories –P 3 M Continuum background –Implicit water Scattering –Thermalizes ions Finite size of the ions F

National Center for Design of Biomimetic Nanoconductors R eza T oghraee initialize ( t = 0 ) grid, protein charges calculate  fixed r ions   ions solve POISSON update E Move ions (E + F LJ ) scattering with water scattering off protein/lipid update r ions ~ short range forces ~ t  t +dt Lennard Jones 6-12 potential P3MP3M LJ

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Complexity of Monte Carlo Simulations for Typical Ion Channels Very large domains and very few particles electrodes lipid (  =2) protein (  =20) 96Å electrolyte (  =80) side view 96Å lipid (  =2) protein (  =20) aqueous pores (  =80) cross-section

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Complexity Continued… Very large simulation times –Time multi-scale problem Ergodicity –MOCA is based on random numbers

National Center for Design of Biomimetic Nanoconductors R eza T oghraee High Throughput Simulations IV curves –Bias –Ionic concentrations –Ionic species Different protein configurations –Crystallographic configurations Mutations etc …

National Center for Design of Biomimetic Nanoconductors R eza T oghraee NanoHUB and Grid Application How we use Grid – i.e. OSG, or TeraGrid –NCN account (nanoHUB) –Demo version of Rappturized BioMOCA –Coupling nanoHUB with the Grid Automatic access and job lunching for non-experts

National Center for Design of Biomimetic Nanoconductors R eza T oghraee Recent Application Simulation of the Mechanosensitive Channel of Small Conductance (MscS) Impractical with Molecular Dynamics In collaboration with Prof. Klaus Schulten’s group, Theoretical and Computational Biophysics (TCB) at Beckman Institute, UIUC. Periplasm Cytoplasm

National Center for Design of Biomimetic Nanoconductors R eza T oghraee MscS Continued Biophysical Journal 90: , 2006.

National Center for Design of Biomimetic Nanoconductors R eza T oghraee OSG Experience with BioMOCA Several protein configurations of MscS channel –Truncated protein –Hydrated lipid 1800 runs on OSG i.e.  Truncated protein without lipid hydration  K + Cl - at 100, 200, 500 milli molar concentrations  Filter selectivity: 100 milli molar / 100 milli volts: K + L->R: 0 & R->L: 5 Cl - L->R: 75 & R->L: 1 Total current of 79 electron charges during 72 nano seconds