# Presentation: 081200

## Scalable Molecular Dynamics

- T.P.Straatsma
- Laboratory Fellow and Associate Division Director
- Computational Biology and Bioinformatics
- Computational Sciences and Mathematics Division
- Pacific Northwest National Laboratory

## NWChem Molecular Science Software

## Domain Decomposition

## Force Evaluation

## Particle-mesh Ewald

***1. Charge grid construction***
***2. Block to slab decomposition***
***3. 3D-fast Fourier transform***
***4. Reciprocal space energy & forces***
***5. 3D-fast Fourier transform***
***6. Slab to block decomposition***
***7. Atomic forces***

## Flowchart

## Timing Analysis

***Haloalkane dehalogenase, force evaluation timings***

## Load Balancing

***Collective***
***Resizing ***

## Dynamic Load Balancing

## Challenges for the DOE

- Environmental Legacy at Hanford and other DOE sites
-  Bioremediation

- Environmental and Health Impact of Energy Use
-  Carbon sequestration
-  Nitrogen fixation

- Production of Energy
-  Biofuels
-  Hydrogen

## Molecular Basis for Microbial Adhesion and Geochemical Surface Reactions

- Microbes in the subsurface mediate a number of environmental, geochemical processes:
- Uptake of metal ions, including environmentally recalcitrant metals
- Adhesion to mineral surfaces
- Reduction and mineralization of ions at the microbial surface
*Pseudomonas aeruginosa*: 	**Cu**, **Fe**, Au, **La**, **Eu**, **U**, Yb, Al, **Ca**, Na, K
*Shewanella putrefaciens*: 		Fe, S, Mn
*Shewanella alga*: 			Fe, Cr, Co, Mn, U
*Shewanella amazonensis*: 		Fe, Mn, S
*Shewanella oneidensis MR1**	*External reduction involving OM cytochromes

## Project Objectives

- Molecular level characterization of:
- Microbial adhesion to mineral surfaces
- Metal ion concentration in microbial membranes
- Focus on Gram-negative bacterial Outer Membrane
- Computational Approach:
- Molecular modeling and molecular dynamics simulations
- Quantum mechanical description of key functional groups
- Thermodynamic Modeling

## Gram Negative Cell Walls

## LPS of Pseudomonas aeruginosa

- 1. Design of the Rough LPS Molecular Model
- 2. Determination of Electrostatic Model

## LPS Membrane Construction

- Distribution of functional groups and water in the outer membrane of *P. aeruginosa*.
- These results are used for thermodynamic modeling of ion adsorption in microbial membranes.

## Phosphate Clustering

- Outer Core

- Inner Core

- These results lend support to the interpretation of recent XAS experiments carried out by J. Bargar at SLAC indicating that uranyl ions take up by microbial membranes exists in clusters involving phosphates.

## Membrane Electrostatic Potential

- Average Potential Across Membrane
- 	Calc.:	100 mV
- 	Exp.:	  80 mV

## Atomic Charges from 2D SCF-HF ESP Fit

## Membrane-Mineral Interactions

## P. Aeruginosa Outer Membrane Proteins

*E. coli* membrane protein FecA (Pautsch and Schultz, 1998) and homology modeled *P. aeruginosa* membrane protein FecA (Straatsma, unpublished)

*E. coli* membrane protein TolC (Pautsch and Schultz, 1998) and homology modeled *P. aeruginosa* membrane protein OprM (Wong et al., 2001)

*E. coli* membrane protein OmpA (Pautsch and Schultz, 1998) and homology modeled *P. aeruginosa* membrane protein OprF (Brinkman et al., 2000)

## P. aeruginosa OprF

## Electron transfer in bacterial respiration

- Under anaerobic conditions, *Shewanella frigidimarina* is able to use extra-cellular iron as the electron acceptor in its respiration.   The electron transfer pathway involves a number of cytochromes which deliver electrons from the cytoplasmic membrane to the periplasmic membrane, where iron reduction occurs.
- The electron transfer (ET) between the membranes is carried out by the respiratory enzyme flavocytochrome c3 fumarate reductase (Fcc3), which contains four *bis*(histidine) hemes.

## Electron Transfer in Fcc3 and Ifc3 

- Flavocytochrome c3 fumarate reductase of *Shewanella frigidimarina*

## Marcus’ theory of electron transfer

## B3LYP Characterization of a model heme

_**ET donor/acceptor orbital d**__**π**_

## Computational Structural Biology Challenges

-  Protein-protein complexes: cell signaling
-  Protein-membrane and mineral-membrane complexes
-  Extension to microsecond simulation times
-  Statistically accurate thermodynamic properties
-  Comparative trajectory analysis
-  Enzyme catalysis using hybrid QM/MM methods
-  Extension toward millisecond simulation times
-  Protein folding and unfolding
-  Membrane transport of simple ions and small molecules
-  Membrane fusion, vesicle formation
-  Scalability on next generation MPP and hybrid architectures

**Computational Structural Biology Challenges**

## Acknowledgements

- Dr. Roberto D. Lins, ETH Lausanne, CH
- Dr. Robert M. Shroll, Spectral Sciences, Boston, MA
- Dr. Wlodek K. Apostoluk, Wroclaw University, Poland
- Dr. Andy R. Felmy, Chemical Sciences Division, PNNL
- Dr. Kevin M. Rosso, Chemical Sciences Division, PNNL
- Professor David A. Dixon, University of Alabama
- Dr. Erich R. Vorpagel, EMSL
- DOE Office of Advanced Scientific Computing Research
- DOE Office of Basic Energy Science, Geosciences Research Program
- DOE Office of Biological and Environmental Research
- EMSL Molecular Sciences Computing Facility
- 	Computational Grand Challenge Application Projects