1. Alessandro Pedretti A new distributed paradigm for parallel computing UNIVERSITÁ DEGLI STUDI DI MILANO Facoltà di Scienze del Farmaco

2. Typical scenario in a lab Internet Firewall Servers PCs Network devices Ethernet infrastructure 100-1000 Mbit/s Several PCs with heterogeneous hardware / OSs. Very high computational power “fragmented” on the local network. Hard possibility to use all computational power to run a single complex calculation.

3. Parallel computing without cluster paradigm. Client/server architecture with hot-plug capabilities. Possibility to perform calculations with different pieces of software without changing the main code. Expandable by scripting languages. High-level database interface integrated in the main code and supporting the most common SQL database engines (Access, MySQL, SQLite, SQL Server, etc). Easy configuration by graphic interface. High performances and security. Main features

4. … to develop WarpEngine: What we need … High-level database interface. Fast customizable Web server. Script engine. Graphic environment. Plug-in expandability Scripting languages Molecule editing Surface mapping File format conversion Database engine Graphic interface Property calculation MM / MD calculations Trajectory analysis

5. Server scheme UDP serverHTTP server Client manager Project manager Job manager VEGA ZZ core Database engine IP filter PowerNet plug-in Main program To clients TCP/IP, HTTP, broadcast Optional encrypted tunnel provided by WarpGate

6. Project manager - server Parser module Server script Script compiler XML project Server module Event handler Actions Initialization Client connection Data dispatch Data receive Resource cleanup Validation Job managerClient manager Tcc – HyperDrive powered

7. Client scheme UDP clientHTTP client Project manager Multithreaded worker VEGA ZZ core PowerNet plug-inMain program To the server TCP/IP, HTTP, broadcast

8. Project manager - client XML parser Client script Script compiler XML project Client module Multithreaded worker Actions Download / check of files HTTP client Tcc – HyperDrive powered Project manager To the server Job end check GET / POST methods

9. Graphic interface

11. Hardware for the test 1 PC configured as client and server: Quad-core 9 PC configured as client: 1 six-core 7 quad-core 1 dual-core 1 single-core 37 cores 42 Gb ram > 3 Tb storage Operating systems: 6 Windows 7 Pro x64 3 Windows 7 Pro 1 Windows XP Pro Network connection: Ethernet 100 Mbs

12. Communication stress test: delivery of empty jobs to the clients and receive of the result from them. 79.651,78 jobs / min. Preliminary performance test Database stress test: extraction (by SQL query), decompression and delivery of molecules to the clients and answer. 41.115,00 molecules / min. Apache Bench 2.0.41 100 requests with concurrency level of 5. 3.205,13 pages / sec. 1,560 ms / request Microsoft IIS 6.0 1.066,67 pages / sec. 4,688 ms / request

13. Software & data for the test APBS – Adaptive Poisson-Boltzmann Solver Calculation of solvation energy. PLANTS – Protein-Ligand ANT system Structure-based virtual screening. Database of drugs in.mdb format 174.398 molecules, average MW 353,70. Human M2 muscarinic receptor PDB ID: 3UON. Both programs are single-threaded

14. APBS – Solvation energy calculation. 174.398 molecules, two APBS calculation for each molecule (reference and solvated state). Time required by a single thread calculation: 13 days 5 hours Time required by WarpEngine: 8 hours 36 minutes WarpEngine speed: 339,10 jobs / min. Real case tests PLANTS – Virtual screening. 174.398 molecules, M2 target, search speed 2. Time required by a single thread calculation: 36 days 22 hours Time required by WarpEngine: 1 day 0 hour 1 minute WarpEngine speed: 121,00 jobs / min.

15. WarpEngine is easy expandable by scripting language, so it’s possible to add some other calculation types: The future … Semi-empirical calculations  MOPAC Ab-initio calculations  FireFly / PC GAMESS Other virtual screening methods  AutoDock, Vina Rescore of docking poses  VEGA, XScore Molecular mechanics calculations  AMBER, AMMP, NAMD Other applications …