ACEnet: Modeling & Simulation Resources for Natural Products

1. Introduction to ACEnet: modelling and simulation resources for natural products modelling Dr. Mohamed ShajahanGulamRazul, Computational Research Consultant

2. What is ACEnet? # Consortium of Atlantic Canada universities # Canada Foundation for Innovation (CFI) is the principal funding source • # High-performance computing facility • * Hardware • Computing – visualization – communication • * Software • * Expertise

3. Where is ACEnet? Member institutions

4. Where is ACEnet? Member institutions Current compute nodes hosting institutions Cluster name:Placentia Cluster name: Fundy,Courtenay (UNB-SJ) Cluster name: Brasdor Cluster name: Glooscap Cluster name: Mahone

5. Hardware: Processors - 2.6 - 3.0 GHz dual-core AMD Opterons quad-core AMD Opterons* Linux - Red Hat Enterprise Linux 4.8 10G-Myrinet 10G GigE - Gigabit Ethernet 2K - Myrinet 2000

6. Storage: Main Storage Global Scratch No-Quota Scratch

7. Other Facilities Internet videoconferencing (inSORS / AccessGrid)- Dalhousie - Memorial - Mount Allison - Saint Mary’s - Saint Francis XavierAcadia - New Brunswick + other sites across Canada & the world

8. Other Facilities Data cave new! 3D immersive data exploration facility (SMU)

9. Other Facilities Data cave 3D immersive data exploration facility (SMU)

10. How do I get started?Getting an account: http://www.ace-net.ca/

13. connection between material properties and constituent atoms and molecules. From a chemical perspective…. • Creation of new materials for science and engineering • Exploiting the nano-world through understanding of control processing, structure and properties • Exploration and development of the frontier between materials and biology. theory Achieved through a synergistic combination of theory, computation and experiment experiment computation

14. *First principles material modelling in industry to decide on important outcomes* *modified from Geder C. and Marzari N. - Atomistic computer modelling of materials, 2005 - MIT **Computer aided drug design **Hardy, L.W. and Malikayil, A., Current Drug Discovery, 2003, December 15-20 The impact of structure-guided drug design on clinical agents. **Cheatham III, T. E. Do bigger or longer simulations of DNA actually teach us anything new?

15. SOFTWARE

16. Gaussian 09 Highlight some new chemistry calculations possible with this version. • ONIOM method: (electrostatic properties of the region treated by Molecular mechanics (MM) can be simultaneously during calculations on the QM region.)-includes a MM program with Gaussian 09 • Polarizable Continuum Model (PCM) for modeling system in solution. This approach represents the solvent as a polarizable continuum and places the solute in a cavity within the solvent. • Two flavours of Molecular dynamics- BOMD (Born-Oppenheimer MD) and ADMP (Atom-centered Density Matrix Propagation). • Calculation of excited states: accurate two to many electron excited states for organic molecules and in the presence of solvents (PCM approach) • Some new calculations of molecular properties:spin-spin coupling constants, g tensors and other hyperfine spectra tensors, Harmonic/anharmonic vibration/vibration-rotation coupling, Optical Rotations/Optical Rotary Dispersion….

17. GAMESSGeneral Atomic and Molecular Electronic Structure System • Developed my Mark Gordon and co-workers at Iowa state university (www.msg.ameslab.gov/GAMESS/) • Performs many electronic structure calculations (similar to Gaussian) - Dynamic reaction coordinate (modify kinetic energy to system at any geometry, add photon(s) to any vibrational mode and have classical trajectory utilizing QM derived energies) - Monte Carlo sampling to find global minimum. - Calculations of Nuclear and spectroscopic properties - well developed QM/MM methods -effective fragment method ( a few hundred fragments can be defined) -For surface chemistry , the surface integrated molecular orbital molecular mechanics(SIMOMM), applied recently to growth of diamond and silicon carbide surfaces

18. CPMDCar-Parinello molecular dynamics CPMD consortium established in 2001, coordinates the development and distribution of the code. Organization coordinated by M. Parrinello and W. Andreoni (www.cpmd.org) Use plane wave/psuedopotentials implementation of DFT for electronic degrees of freedom and Molecular dynamics (usually used for liquids). Properties calculated: -MD calculations in constant energy, temperature and pressure ensembles. -Ionic positions, velocities and energies of complete trajectory. -The evolution of stress tensors, the unit cell, constraint forces and dipole moments. -Configuration and conformations of all constituent atoms and molecules -Nuclear quantum effects my be investigated via Path-Integral MD -Vibrational properties.

19. DL_POLY Developed by by W. Smith, T.R. Forester and I.T. Todorov in 1993 at Daresbury Laboratory, UK. A general purpose molecular dynamics program. (www.cse.scitech.ac.uk/ccg/software/DL_POLY/) DL_POLY2 - 30,000 atoms on up to 100 cores DL_POLY3 - 1,000,000 atoms from 8-1024 cores 1.Simple atomic systems and mixtures e.g. Ne, Ar, Kr, etc. 2.Simple unpolarisable point ions e.g. NaCl, KCl, etc. 3.Polarisable point ions and molecules e.g. MgO, H2O etc. 4.Simple rigid molecules e.g. CCl4, SF6, Benzene, etc. 5.Rigid molecular ions with point charges e.g. KNO3, (NH4)2SO4, etc. 6.Polymers with rigid bonds e.g. CnH2n+2 7.Polymers with rigid bonds and point charges e.g. proteins. 8.Macromolecules and biological systems. 9.Molecules with flexible bonds. 10.Silicate glasses and zeolites. 11.Simple metals e.g. Al, Ni, Cu etc.

20. GROMACSGroningen Machine for Chemical Simulations • GROMACS was first developed in Herman Berendsens group (late 90’s) in the department of Biophysical Chemistry of Groningen University. Head authors & project leaders: Erik Lindahl (Stockholm Center for Biomembrane Research, Stockholm, Sweden), David van der Spoel (Biomedical Centre, Uppsala, Sweden) and Berk Hess (Max Planck Institute for Polymer Research, Mainz, Germany),(www.gromacs.org) • It is primarily designed for biochemical molecules like proteins and lipids that have a lot of complicated bonded interactions • GROMACS is extremely fast at calculating the non-bonded interactions (that usually dominate simulations) many groups are also using it for research on non-biological systems, e.g. polymers. Can simulate millions of atoms • Can perform molecular dynamics, stochastic dynamics (Brownian) and energy minimization

21. GROMACS • The package includes a fully automated topology builder for proteins, even multimericstructures. Building blocks are available for the 20 standard amino acid residues as well as some modified ones, the 4 nucleotide and 4 deoxynucleotide residues, several sugars and lipids, and some special groups like hemes and several small molecules. • Highly parallelized code enables easy implementation of large multi-core jobs • Post processing of simulations comes with a suite of analytical tools for detailed examination of large biomolecular molecules: • For example: - Easy separation of chemically distinct groups for analysis - comes with built in trajectory viewer (ngmx) - normal mode analysis - computes Ramachandran plots - structural measures like radial distribution functions provided - various correlation functions - covariance analysis - radius of gyration calculations

22. Where to go for help • ACEnet User Guide • http://www.ace-net.ca/wiki/User_Guide#ACEnet_Overview • Research/user support personnel • email: support@ace-net.ca

23. Acknowledgments Canada Foundation of Innovation (CFI) National Science and Engineering Research Council (NSERC) Atlantic Canada Opportunities Agency (ACOA) The research and innovation initiatives of Nova Scotia, New Brunswick and Newfoundland and Labrador Greg Lukeman, CTO ACEnet- Compute Canada Darren Derksen