1. Molecular dynamics of DNA fragments on the Grid Kirill Zinovjev Latvian Institute of Organic Synthesis Riga Technical University 2009. g.

2. 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)

3. Molecular dynamics T=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)

4. „E-box” biological function c-Myc-Max heterodimer binding → TRRAP coactivator transporting to MBII domain → Histone acetilation by HAT → Gene activation and expression

5. RTU ETF Grid (Latvia) CYFRONET (Poland) Methods Molecular dynamics NMR NOESY Varian Unity INova 600 MHz

6. Software NAMD – molecular dynamics calculation XPLOR – theoretical spectra calculation VMD – simulation system preparation, molecular dynamics trajectory visualization and analysis Freeware! NAMD, VMD – Open Source

7. 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)

8. Results 5’-CGCACGTGCG-3’ A4 incorrectly predicted NOE’s

9. Unique E-box features Distance between central nucleotides 5’-CGCAC(3.35 Å)GTGCG-3’ Unique sodium binding site Increased hydration

10. 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

11. Future Molecular docking for medicinal chemistry QM/MM simulations Simulations of proteins, membranes and their complexes

12. Acknowledgements BalticGrid project (www.balticgrid.org), especiallywww.balticgrid.org Janis Kulinsh and Lauris Cikovskis (RTU ETF)

13. Thank you!!!