Peptide Folding

Movie Time

Protein Physics Structural Change

Petascale Future

Computer Simulation - Basic Principles

Molecular Mechanics Potential

ji ij

ji

ji ij

ij

ij

ijij

impropersdihedrals

N

n

n

anglesbondsb

Dr

qq

rr

KnK

kbbkV

,,

612

20

1

20

20

4

cos1

Model System

QuantumMechanical

MolecularMechanical

or QM/MM Potential

Simulation - exploring the energy landscape

Reactant

Product

Energy Landscape

Halorhodopsin - Chloride Pumping at Atomic Resolution

ANDREEA GRUIA

Not Enough Room

Structure 13 617 (2005).

Spring-loaded throttle valve helps prevent chloride leakage

.

Barrier without valve= EII = 13 kcal/mol.

Sum = 25 kcal/mol = no backflow.

Valve Energy= EI = 12 kcal/mol

Muscle Contraction

Thick filamentThin filament

ATP Hydrolysis by Myosin

SONJA SCHWARZL

Biochemistry 45 5830 (2006)

04/21/23 MSBIO - Universität Heidelberg 10

Dynamics of Muscle Contraction.

BJORN WINDSHUEGEL

PNAS 102 6873 (2005)

ns range

s range

reactant product

FRANK NOE

Large-Scale Functional Conformational Transitions

GTP-Bound Form (ON)

GDP-Bound Form (OFF)

Ras p21

GTP-Bound Form (ON)

Ras p21

Ras p21 trajectoryFRANK NOE

reactant product6

25

1

76

28

13 811

57

9

3

18

FRANK NOE

J. Chem. Phys. 126 155102 (2007)

Sampling: Uniform Distribution

Sampling:Exclusion of „Bad Structures“

Sampling:Fail-Fast Minimization

Sampling:Increase Density of Low-Energy Points

Transition Network:Edges between Neighbours

Connectivity of Network of Best Paths

Tem

pera

ture

Ras Molecular SwitchON - state OFF - state

Cray XT4

SpallationNeutronSource

ExpensiveToys

Cray XT4

One Million Atoms – Molecular Dynamics

Lars Meinhold

Zoe Cournia

Lignocellulosic Biomass Exhibits Lignocellulosic Biomass Exhibits

Structural ComplexityStructural ComplexityO

O

O OAc

O

O

HO

OAcO

HO

O

O

O

AcO

OH

O-XylanO

O

HOOAc

O

O

AcO

OAcO

O

HO

HO

OHO

OHO

HO OH

HO

O

O

HO

OH

O

O

O

H3CO

OH

OH

OH

OH

OH

OCH3

HO

OCH3

O

HO

HO

H3CO

OHO

HO OCH3

O

HO

OCH3

O

HO OH

O

OH3CO

HO

HO

O

OH

OH

OCH3

OCH3

OH

OH

O

OCH3

OO

OCH3

O

OCH3

HO

HO

OCH3

O

O

OCH3

HO

O

HO

HO

OCH3

Hemicellulose

Lignin

Cellulose

Cray XT4

SpallationNeutronSource

Molecular Simulation Molecular Simulation ProjectsProjects

Cellulose.

Lignin.

Lignocellulosic Biomass.

Cellulase Reaction Mechanism.

Cellulosomes (subsequent talk).

Flopsideal

• Gromacs with Reaction-Field• 5.4 million atoms, 175 atoms/core

10 1,000 100,0000.1

1

10

100

Strong Scaling

cores

TF

lops

Now

5 years ago

Computer Power Improvement for Computer Power Improvement for Biological Molecular Dynamics Biological Molecular Dynamics SimulationSimulation

Cellulose I + 26 lignins

Probe for factors that might influence recalcitrance cellulose accessible surface area radii of gyration of lignins

Softwood Lignin & CelluloseSoftwood Lignin & Cellulose

Large-Scale Molecular Dynamics Simulation (1-3M atoms) using 2008 DOE INCITE award on ORNL Cray XT4.

Cellulose: Cellulose: Benjamin LindnerBenjamin Lindner

Preliminary Findings

7 ns

Crystalline

1 ns

Crystalline/Amorphous

Collaborators

UT/ORNL Center for Molecular Biophysics

• Maramuthu Krishnan (CMB, ORNL)• Loukas Petridis (CMB, ORNL)• Jiancong Xu (CMB, ORNL)• Roland Schulz (CMB, ORNL)• Benjamin Lindner (CMB, ORNL)

External

• Nicoleta Bondar (U. Cal Irvine)• Lars Meinhold, Ahmed Zewail (Caltech)• Kei Moritsugu (RIKEN)• Akio Kitao (U. Tokyo)• Stefan Fischer, Isabella Daidone (U. Heidelberg)• Torsten Becker (U. Bayreuth)• Frank Noe (Free University of Berlin).• Vandana Kurkal-Siebert (BASF, Ludwigshafen).• Franci Merzel (U. Ljubljana)• John Finney (U. London)• Roy Daniel (U. Waikato)• Andrea Amadei, Alfredo Di Nola (U. Rome “La Sapienza”)