PRAGMA Avian Flu Grid: Drug Discovery against Infectious Diseases

Wilfred W. Li, Ph.D., UCSD, USA

Habibah Wahab, Ph.D., USM, Malaysia

Accumulative Statistics on H5N1

http://www.wpro.who.int/sites/csr/data/data_Maps.htm March 19, 2008

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

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

Software Status from SCMSWeb

Vision Based Grid Workflow Environment

Clementi et al, IEEE eScience 2008

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

Glyco-Mgrid and VS-Mgrid

Youngjin Choi, Karpjoo Jeong

Glycobiology of Neuraminidase

• Sharing of simulation data

• Sharing of knowledge and expertise

Crystal MD-CHARMM MD-NAMD

Youngjin Choi

NA active site domain is intrinsically flexible and offers new drug design opportunities

Top Hits

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

Visualization of HA-Glycan Interactions

Xu, et al. JMB, 2008 (submitted).

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

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.

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