FKPPL workshop May 2012 BUI The Quang Prof. Vincent Breton Prof. Doman Kim Prof. NGUYEN Hong Quang Prof. PHAM Quoc Long Grid enabled in silico drug discovery

FKPPL workshop, May 2012 Laboratories involved -CNU, Gwangju, Korea -IFI, Hanoi, Vietnam -INPC, Hanoi, Vietnam -KISTI, Seoul, Korea -LPC, Clermont-Ferrand, France 2

FKPPL workshop, May 2012 Content Activity in Korea Activity in Vietnam Activity in France 3

FKPPL workshop, May 2012 Human maltase: - A α-glucosidase, belongs to glycosides hydrolase family 31 (EC and ) and located on chromosome 7 with 868 amino acids and contains five distinct protein domains. - Important target in treatment of diabetes type 2. Credit: Doman Kim Activity in Korea - Publication 1 4

FKPPL workshop, May 2012 Scoring based on docking score ( 308,307) Scoring based on docking score ( 308,307) 454,000 chemical compounds from Chembridge Interaction with key residues 3016 compounds selected 2616 compounds selected Key interactions binding models clustering Key interactions binding models clustering In vitro test 42 compound selected Filtration process Total numbers of docking308,307 Total size of output results16.3 GB Estimated duration by 1CPU22.4 years Duration of experiments3.2 days Maximum numbers of concurrent CPUs4700 CPUs Crunching Factor2556 Distribution Efficiency54.4 % Statistics of data challenge deployment on WISDOM production environment Credit: Doman Kim 5

FKPPL workshop, May 2012 Inhibition on human maltase & pancreatic α-amylase Compound No. Lowest Energy M.W (g/mol) Ki (μM) IC 50 (µM) Type of inhibition ±1.258±4Competitive ±0.955±3Competitive Acarbose ±4Competitive Unlike acarbose, compounds 17 and 18 were competitive inhibitors exclusively for HMA without any in vitro inhibition for human pancreatic alpha-amylase. Credit: Doman Kim 6

FKPPL workshop May )A global outbreak of Severe Acute Respiratory Syndrome (SARS) between March 2003 and July 2003 caused over 8,000 cases and 774 deaths (9.6%) (World Health Organization). 2)The 3C-like protease (3CL pro ) is needed for SARS-CoV replication and is a promising drug target. World Health Organization. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003 (based on data as of the 31. December 2003). Activity in Korea - Publication 2 Credit: Doman Kim

FKPPL workshop, May 2012 Docking parameters: Ga_run=50, Ga_pop_size=250, Ga_num_generation=27000, Ga_num_evaluation= Virtual screening on WISDOM production environment Virtual screening 3CL protease of SARS on WISDOM production environment 54 compounds were selected for In vitro assay 308,307 compounds Compound NoFree binding energy (kcal.mol -1 ) IC 50 (μM) ± ± ± ± ± ± ± 1.17 Credit: Doman Kim 8

FKPPL workshop, May 2012 Activity in Vietnam The WPE platform –Used in WISDOM projects(Wide In Silico Docking On Malaria) for discovery of medicine for malaria –Developed by LPC Clermont-Ferrand laboratory –Reduce many time for finishing these challenges The DIRAC platform –DIRAC: Distributed Infrastructure with Remote Agent Control –DIRAC forms a layer between a particular community and various compute resources to allow optimized, transparent and reliable usage Comparison between the WPE & DIRAC platform –Performance –Stability –Capability of submission of pilot agent 9

FKPPL workshop, May 2012 Comparison of performance DIRAC is faster than WPE WPE is faster than DIRAC  DIRAC submit faster pilot agent than WPE  one WPE’s agent execute many task while one DIRAC’s agent execute only one task DIRAC is faster than WPE WPE is faster than DIRAC 10

FKPPL workshop, May 2012 Comparison of stability Percentage of DIRAC pilot agent is terminated by unknown cause is less than WPE platform  Pilot agent of DIRAC is more stable than pilot agent of WPE Rate of WPE’s & DIRAC’s pilot agents is terminated by unknown cause(test with Autodock) 11

FKPPL workshop, May 2012 Comparison of capability of submission of pilot agent Rate of DIRAC pilot agent submission successful to grid is higher than WPE platform  DIRAC platform submits better pilot agent to grid than WPE platform Rate of pilot agent submission successful to grid 12

FKPPL workshop, May 2012 Result from INPC laboratory Database of natural products isolated from biodiversity in Vietnam (~1000 ligands) Anti-malarial tests on 43 compounds with 2 biological targets: chloroquine-susceptible T96 and chloroquine resistant K1 Ongoing research to look for compounds with anti- malarial bioactivity by virtual screening on the database of natural products (2011) –Key protein: protein plasmepsin II (1LEE) –Use of AUTODOCK software for virtual screening 13

FKPPL workshop, May 2012 Activity in France Design a virtual screening system for multi-user Scheduler Grid resource Problem of virtual screening on grid -Speed of machine are different -Task arrive in random process -Available duration of machine are random  Find out the policy for maximizing the throughput of all users Workflow of research -Find out the policy and prove by theory -Valid on the grid simulator SIMGRID -Programming scheduler on the DIRAC platform 14

FKPPL workshop, May 2012 Thank you for your attention 15