Presentazione di PowerPoint

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Tubulin Monomer Mechanical Properties Obtained by
Simulating Atomic Force Microscopy Experiments
Using Molecular Dynamics
PhD student Søren Enemark
Supervisors Prof. A. Redaelli Ing.
S. Monica
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Introduction What am I talking about?
aß-tubulin dimer
Hetero dimer
2 x 450 residues
Subunit in MTs
Microtubules (MTs)
Length 1-10µm
Cylinder-shaped
Lattice structure
Rot. trans. symmetry
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Introduction What are microtubules good for?
MTs main functions

• Structural elements
• Intracellular transport
• Cell division

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Modeling Stress-strain directions
Single monomer mechanical properties
MT mechanical properties
Compression
Elongation
4 tests for each monomer
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Modeling Stress-strain directions (contd)
Directions depend on the MT structure
Longitudinal interactions
Along straight line
13.8
Lateral interactions
Atomic structure by K. Downing
Basic structure 1JFF.pdb
Fitted to MT structure data
Monomer centre-of-mass (CM)
End view on MT
Along lines towards CM of lateral monomers
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Procedure Preparing the structure
Monomer structure extracted
1.
Arrange in box w/ SPC water
2.
Dodecahedron box
System size
37,000 (SOL)
4,500 (monomer)
MD
Pull groups position restraints
4.
Twin-range cut-off
Parameters
rvdw 1.4 rcoulomb1.4
rlist 0.8 nstlist 5
Berendsen thermostat
SOL monomer
Two groups
?tau 0.1 ps
Tref 300 K
All-bonds constraints, Lincs
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Preparing AFM-like MD
Pull groups

• residues lt 8 ? from interacting monomer
• In longitudinally tests 731 and 675 atoms
• In laterally tests 188 and 198 atoms

Retain interface structure, but generate new
configurations
Position restraint pull groups
1000 ps
0 ps
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AFM-like MD how to measure the stiffness
AFM-like Method
Typical results (pulling)
Pull group P1
Pull group P2
S1
P1
Spring S2
Spring S1
P2
S2
Spring stiffness
103 kJ/(nm2 mol) 1.67 nN/nm
Spring velocity
(7-11 simulations)
v5 10-3 nm/ps
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Single monomer - MD results
?-tubulin pulling - longitudinally
Linear fit y(x) a x b
F (nN)
0.50
v5 10-3 nm/ps
0.25
?l (nm)
F (nN)
a 5.20.4 nN/nm
b 0.40.1 nN
v5 10-3 nm/ps
?l (nm)
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Single monomer - MD results
Longitudinally
Laterally
v5 10-3 nm/ps
Elongation
Compression
Elongation
Compression
a-tubulin
ß-tubulin
Monomers are more rigid longitudinally than
laterally
Monomer might be less rigid under elongation than
compression
a-tubulin might be less rigid then ß-tubulin
longitudinally, but more rigid laterally
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Simplified MT model a bed of springs
a-, and ß-tubulin stiffness monomer-to-monomer
interactions
MD
Elastic constants
FEM
Axial tests on 1 µm MT
Tubulin Monomer Interaction Study by Molecular
Dynamics Simulation
POSTER
Marco Deriu et al.
EST Marie Curie programme contract No.
MEST-CT-2004-504465
Active BIOMICS STREP project contract No.
NMP4-CT-2004-516989