pragma avian flu grid: drug discovery against infectious diseases wilfred w. li, ph.d., ucsd, usa...
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PRAGMA Avian Flu Grid: Drug Discovery against Infectious Diseases
Wilfred W. Li, Ph.D., UCSD, USA
Habibah Wahab, Ph.D., USM, Malaysia
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Accumulative Statistics on H5N1
http://www.wpro.who.int/sites/csr/data/data_Maps.htm March 19, 2008
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Transparent access of applications on Avian Flu Grid through middleware
Gfarm File System
applications
databases
/gfs/$USER
NAMDAutoDock
Zinc NCIDS
Virtual Directory Tree
H5N1 related glycan conformation analysis
using M*Grid and Glyco-M*Grid
Relaxed Complex Method Molecular
Dynamics Simulation Data Sets & Database
Virtual Screening Data Sets & Database
PRAGMA PortalMy WorkSphere
CSF4 Server
HPC Clusters, NBCR,
TeraGrid, MHPCC
Mr. Bayes
Opal poster, PRAGMA 13
AFG poster, PRAGMA 13
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Opal CSF4 Integration Cluster
Cluster
Cluster
App X
App YOther
Resource
12 CPUs
App X
App Z
Other Resource
64 CPUs
App Y
App Z 8 CPUs
Other Resource
C SF 4 M eta-Sch ed u l er
Resource Status L ist
M DS
Resource
Scheduling M odules
Resource Requirements
App X10 CPUs
App Z40 CPUs
App X5 CPUs
App Y1 CPU
Tomcat Container
Axis Engine
Opal WS Opal WS
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Software Status from SCMSWeb
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Vision Based Grid Workflow Environment
Clementi et al, IEEE eScience 2008
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Data visualization
________________________________________________________________________________ | | | | | Clus | Lowest | Run | Mean | Num | Histogram -ter | Binding | | Binding | in | Rank | Energy | | Energy | Clus| 5 10 15 20 25 30 35_____|___________|_____|___________|_____|____:____|____:____|____:____|____:___ 1 | -6.78 | 10 | -6.70 | 6 |###### 2 | -6.51 | 5 | -6.14 | 4 |#### 3 | -6.39 | 59 | -6.08 | 6 |###### 4 | -6.34 | 6 | -6.08 | 10 |########## 5 | -6.27 | 87 | -6.04 | 4 |#### 6 | -6.02 | 83 | -5.94 | 9 |######### 7 | -5.98 | 61 | -5.74 | 4 |#### 8 | -5.82 | 19 | -5.82 | 1 |# 9 | -5.67 | 9 | -5.64 | 2 |## 10 | -5.51 | 32 | -5.43 | 20 |#################### 11 | -5.50 | 95 | -5.50 | 1 |# 12 | -5.47 | 93 | -5.47 | 1 |# 13 | -5.39 | 27 | -5.37 | 16 |################ 14 | -5.39 | 75 | -5.39 | 1 |# 15 | -5.39 | 16 | -5.35 | 4 |#### 16 | -5.38 | 34 | -5.38 | 1 |# 17 | -5.37 | 77 | -5.37 | 1 |# 18 | -5.31 | 49 | -5.31 | 2 |## 19 | -5.02 | 11 | -5.02 | 1 |# 20 | -4.92 | 74 | -4.83 | 3 |### 21 | -4.76 | 41 | -4.76 | 1 |# 22 | -4.60 | 56 | -4.60 | 1 |# 23 | -4.51 | 90 | -4.51 | 1 |#
process
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Glyco-Mgrid and VS-Mgrid
Youngjin Choi, Karpjoo Jeong
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Glycobiology of Neuraminidase
• Sharing of simulation data
• Sharing of knowledge and expertise
Crystal MD-CHARMM MD-NAMD
Youngjin Choi
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NA active site domain is intrinsically flexible and offers new drug design opportunities
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Top Hits
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Drug Design and Discovery for Developing Countries, 3-5th July, 2008
Compound name Number of conformationFinal Free energy,
kcal/mol Inhibition constant, Ki
MSC 986 39 -11.27 5.35E-09
MSC 1026 15 -12.54 3.45E-09
MSC 1685 1 -12.71 6.29E-09
MSC 1880 2 -15.55 8.58E-10
MSC 1941 6 -12.22 9.42E-10
Top 5 compounds screened from MD trajectories of neuraminidase
MSC986 MSC1026
MSC 1685
MSC 1880 MSC 1941
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Visualization of HA-Glycan Interactions
Xu, et al. JMB, 2008 (submitted).
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Session 1 Summary
• Hoon Choi, KISTI– E-Science Environment for Avian Flu
• PRAGMA 16 – bioinformatics session on flu data integration, epidemiologically
• Data sharing, flu sequence data with China, and other AP countries
• Thanh Truong, U Utah– CSE-online, 2nd generation, Avisto – astonis.com, free for
high school, supported by advertisement– Molecular design, workflow management, connecting
different graphically represented modules– Privately funded development
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More …• Jincheol Kim, KISTI
– DrugScreener-G, Eclipse platform, currently only supports gLite middleware. A platform to support different applications.
– Motuer workflow engine for EGEE; Kepler ?– Support interoperation of gLite, UNICORE.– Will integrate Opal to DrugScreener-G , utilize Gfarm services for data sharing.
• Hongwen Yang, CNIC– Virtual screening database
• Lucy Liu– Qinghai Lake Avian Epidemiological Observerations– Joint Research Center for wild life studies– E-Science demo application
• E-science is a process, not the ultimate goal.
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From here to PRAGMA 16
• Proposed activities towards PRAGMA 16– Large scale SNP analysis – KISTI, J. Kim– Avian Flu workshop– Expanded targets among other infectious diseases– Collaboration with EGEE drug discovery activities