Transcript Boltzmann Transport Monte Carlo Code - BioMOCA Reza Toghraee and Umberto Ravaioli

Boltzmann Transport Monte
Carlo Code - BioMOCA
Reza Toghraee and Umberto Ravaioli
Beckman Institute & ECE Department
University of Illinois at Urban-Champaign
NIH Nanomedicine Center for Design of Biomimetic Nanoconductors
Network for Computational Nanotechnology (NCN) & NanoHUB
BioMOCA code
• Adaptation of the Monte Carlo approach used for solidstate 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.
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
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
Reza Toghraee
http://www.rsc.org/chemsoc/
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
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…
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
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
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
Transport Monte Carlo Particle Simulations
• 3D particle trajectories
– P3M
• Continuum background
– Implicit water
• Scattering
– Thermalizes ions
• Finite size of the ions
F
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
initialize ( t = 0 )
grid, protein charges
calculate fixed
Lennard Jones 6-12 potential
 LJ
~r  
ions
ions
   6   12 
 4 LJ       
 r   r  


1.00
solve POISSON
update E
t  t +dt
short range forces
short range
repulsion
P3M
0.50
Volts
 ( )  (  fixed  ions )
long range
weak attraction
0.00
Move ions (E + FLJ)
scattering with water
scattering off protein/lipid
update ~
rions
Reza Toghraee
 LJ
-0.50
0.0
2.0
4.0
6.0
8.0
10.0
ion separation (Angstroms)
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
Complexity of Monte Carlo Simulations for
Typical Ion Channels
•
Very large domains and very few particles
96Å
96Å
lipid (=2)
lipid (=2)
96Å
protein
(=20)
electrodes
side view
Reza Toghraee
protein
(=20)
electrolyte
(=80)
aqueous
pores
(=80)
cross-section
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
Complexity Continued…
• Very large simulation times
– Time multi-scale problem
• Ergodicity
– MOCA is based on random numbers



1 N 
1
     (t)dt
N 
t


Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
High Throughput Simulations
• IV curves
– Bias
– Ionic concentrations
– Ionic species
• Different protein configurations
– Crystallographic configurations
• Mutations
• etc …
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
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
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
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
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
MscS Continued
Biophysical Journal 90:3496-3510, 2006.
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org
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
Reza Toghraee
National Center for Design of
Biomimetic Nanoconductors
http://www.nanoconductor.org