molecular dynamics of dna fragments on the grid
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Molecular dynamics of DNAfragments on the Grid
Kirill Zinovjev
Latvian Institute of Organic SynthesisRiga Technical University
2009. g.
Molecular Dynamics
• Molecular system simulation on atomic level under given thermodynamic conditions (temperature, volume, pressure)
• Describe system evolution in time
• Capable for biological macromolecules (proteins, nucleic acids, membranes) in water solution
• Calculations are parallelizable (can be performed on the Grid)
Molecular dynamicsT=310° K, P=1 atm
System evolves in time
Theory
Thermodynamics (P,V,T)Newton equation of motion
Molecular mechanics (T = 0° K - absolute zero; P = 0 Pa - vacuo)
...
dihedral
angledistancemolecule
U
UUU
„E-box” biological function
• c-Myc-Max heterodimer binding → • TRRAP coactivator transporting to MBII domain →• Histone acetilation by HAT →
Gene activation and expression
RTU ETF Grid (Latvia)CYFRONET (Poland)
MethodsMolecular dynamics NMR NOESY
Varian Unity INova 600 MHz
Software
• NAMD – molecular dynamics calculation
• XPLOR – theoretical spectra calculation
• VMD – simulation system preparation, molecular dynamics trajectory visualization and analysis
Freeware!
NAMD, VMD – Open Source
Calculations
Input data(Structure, force field parameters, configuration file)
GRID(NAMD 2.6, MPI, 20-40 cores,
≈ 3000 CPU hours)
Temporary results, restart files
Every 3 hours
Storage≈ 6-8 GB each simulation
Final results(trajectory, log file, restart files)
Analysis (VMD, XPLOR)
Results
5’-CGCACGTGCG-3’
A4 incorrectly predicted NOE’s
E-box
0
100000
200000
300000
400000
0 50000 100000 150000 200000 250000 300000 350000
NOE (exp)
NO
E (
teor
)
Unique E-box features
• Distance between central nucleotides
5’-CGCAC(3.35 Å)GTGCG-3’• Unique sodium binding site• Increased hydration
Conclusions and problems
• Selected calculation approach satisfactory describe objects of interest and can be used to investigate the behavior of oligonucleotides in water solution
• The E-box sequence shows several sequence-selective features, that can be used to design substances with high E-box affinity.
• The calculations showed high parallelizability and were succesfully performed on the Grid
• Calculation errors are insufficiently described
• The simulation length is too short (10 ns)
• The CPU utilization dramatically falls, when processes are distributed between too much physical machines
• The calculation time strongly depends on data transfer speed between cores
Future
Molecular docking for medicinal chemistry
QM/MM simulations
Simulations of proteins, membranes and their complexes
Acknowledgements
BalticGrid project (www.balticgrid.org), especially
Janis Kulinsh and Lauris Cikovskis (RTU ETF)
Thank you!!!Thank you!!!
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