Outline GB1 chameleon 8-mer Peptide MD GB1 folding pathway Hierarchic folding Conservation scores.
Peptide Folding
description
Transcript of Peptide Folding
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Peptide Folding
Movie Time
Protein Physics Structural Change
Petascale Future
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Computer Simulation - Basic Principles
Molecular Mechanics Potential
ji ij
ji
ji ij
ij
ij
ijij
impropersdihedrals
N
n
n
anglesbondsb
Dr
rr
KnK
kbbkV
,,
612
20
1
20
20
4
cos1
Model System
QuantumMechanical
MolecularMechanical
or QM/MM Potential
Simulation - exploring the energy landscape
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Reactant
Product
Energy Landscape
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Halorhodopsin - Chloride Pumping at Atomic Resolution
ANDREEA GRUIA
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Not Enough Room
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Structure 13 617 (2005).
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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
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Muscle Contraction
Thick filamentThin filament
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ATP Hydrolysis by Myosin
SONJA SCHWARZL
Biochemistry 45 5830 (2006)
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04/22/23 MSBIO - Universität Heidelberg 10
Dynamics of Muscle Contraction.
BJORN WINDSHUEGEL
PNAS 102 6873 (2005)
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ns range
s range
reactant product
FRANK NOE
Large-Scale Functional Conformational Transitions
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GTP-Bound Form (ON)
GDP-Bound Form (OFF)
Ras p21
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GTP-Bound Form (ON)
Ras p21
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Ras p21 trajectoryFRANK NOE
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reactant product6
25
1
76
28
13 811
57
9
3
18
FRANK NOE
J. Chem. Phys. 126 155102 (2007)
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Sampling: Uniform Distribution
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Sampling:Exclusion of „Bad Structures“
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Sampling:Fail-Fast Minimization
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Sampling:Increase Density of Low-Energy Points
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Transition Network:Edges between Neighbours
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Connectivity of Network of Best Paths
Tem
pera
ture
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Ras Molecular SwitchON - state OFF - state
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Cray XT4
SpallationNeutronSource
ExpensiveToys
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Cray XT4
One Million Atoms – Molecular Dynamics
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Lars Meinhold
Zoe Cournia
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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
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Cray XT4
SpallationNeutronSource
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Molecular Simulation Molecular Simulation ProjectsProjects
Cellulose.
Lignin.
Lignocellulosic Biomass.
Cellulase Reaction Mechanism.
Cellulosomes (subsequent talk).
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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
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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.
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Cellulose: Cellulose: Benjamin LindnerBenjamin Lindner
Preliminary Findings
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7 ns
Crystalline
1 ns
Crystalline/Amorphous
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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”)