peptide folding
DESCRIPTION
Protein Physics. Structural Change. Peptide Folding. Petascale Future. Movie Time. Molecular Mechanical. Quantum Mechanical. Computer Simulation - Basic Principles. Model System. or QM/MM Potential. Molecular Mechanics Potential. Simulation - exploring the energy landscape. - PowerPoint PPT PresentationTRANSCRIPT
Peptide Folding
Movie Time
Protein Physics Structural Change
Petascale Future
Computer Simulation - Basic Principles
Molecular Mechanics Potential
ji ij
ji
ji ij
ij
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impropersdihedrals
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n
anglesbondsb
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KnK
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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)
04/22/23 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”)