Molecular dynamics of DNA fragments on the Grid Kirill Zinovjev Latvian Institute of Organic Synthesis Riga Technical University 2009. g.
Jan 29, 2016
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!!!