Avian Flu Grid
From PRAGMAgridWIKI
Contents |
News
Projec Press Release March 22, 2007
1st Avian Flu Grid Workshop
Aug 6 - 9, 2007 at Honolulu, HI
Hosted by University of Hawaii at Manoa, Honolulu.
Resources & Tools
This project leverages the computational tools and resources contributed by members of the PRAGMA community to develop a global infrastructure for the analysis of Avian Flu as an infectious agent and a pandemic threat.
Computational Resources
Maui High Performance Computing Center
Scientific Research & Resource Development
This project aims to use the grid and high performance computing infrastructure to develop a model for global collaboration in the fight against the pandemic threat of Avian flu and other emerging infectious diseases.
Currently the project focuses on the Hemagglutinin and Neuraminidase proteins from Avian and Human flu viruses in order to understand the mechanism of host selectivity and drug resistance. Through a global partnership forged over the PRAGMA grid development activities, we now aim to build a scalable, global, and open knowledge environment for developing novel inhibitors to avian flu.
In addition, by involving scientific researchers with grid developers, database developers, and leveraging tools and resources from member institutes, we intend to deliver both grid computing tools and data management and sharing capabilities that are tested through cutting edge scientific research, and formulate sustainable models of data sharing and drug discovery through international collaboration.
Specific Aims
The avian influenza virus type A, especially subtype H5N1, is becoming the world's largest pandemic threat due to its high virulence and lethality rate in birds, quickly expanding host reservoir, and high rate of mutations. The two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA) of influenza virus play important roles in the interactions with cellular receptors containing terminal N-acetylneuraminic acid (Neu5Ac, or NANA) moieties, aka, sialic acids. The approved anti-influenza drugs, oseltamivir and zanamivir, inhibit H5N1 infection by targeting the NA active site, thereby blocking the release of newly formed viral particles. However, research has shown that antigenic drift may give rise to new strains that are resistant to existing NA inhibitors and antigenic shift could give rise to new virulent subtypes of the flu virus.
Thus, it is crucial to design novel HA- and NA-targeted inhibitors, which can be used in combination for optimal prophylaxis and treatment. The Relaxed Complex (RC) scheme and Molecular Dynamics (MD) simulations have been applied on the two target proteins to capture key protein dynamics information and accounting for receptor flexibility. Research is under way to take advantage of novel loop flexibilities and changing cavity shapes adjacent to NA active site to discover novel NA inhibitors that may work in a way similar to the HIV integrase inhibitor, raltegravir, inspired by the RC/MD simulation procedures. Further investigation involves statistical cluster analysis for rational selection of representative HA/NA protein structure snapshots, which are used in the virtual screening with synthetic and natural compound libraries. Finally, the binding energies of the high scoring hits are re-scored using Molecular Mechanics-Poisson Bolzmann Surface Area (MM-PBSA) method before experimental validation and subsequent lead optimization.
Methodology and Tools
Relaxed Complex Method
NAMD
Amber
Gromos
Gromacs
Virtual Screening
AutoDock
MGLTools
Resources
The RC/MD workflow is complex and computationally demanding, but with strong potentials for application to other infectious diseases. While the MD simulations are more scalable in a high performance computing cluster with low latency network, the virtual screening process requires little interprocessor communication and is highly suitable for a distributed grid environment. The Avian Flu Grid is an integrative effort based on the technology developed by several member institutes to support advanced scientific research for avian flu.
The calculations based on these state-of-the-art computational approaches is managed by the CSF4 meta-scheduler (http://gcsf.sourceforge.net) through either a portal environment (https://portal.pragma-grid.net:9443) or Opal-based application specific web services (http://nbcr.net/serivces) which leverages CSF4 for job distribution.
Long running MD simulations with a large number of processors are done using TeraGrid (http://www.teragrid.org) resources, and HPC resources available at the National Biomedical Computation Resource (http://nbcr.net), and Maui High Performance Computing Center (http://www.mhpcc.edu). The complex work flows are captured using the Vision workflow management tools (http://mgltools.scripps.edu).
Data
Computational data management and sharing across different sites is simplified using Gfarm (http://datafarm.apgrid.org). The simulation setup, and post-analysis are carried out using M*Grid and Glyco-M*Grid (http://www.mgrid.or.kr/), and virtual screening results are managed using the Scientific Data Grid (http://pragma.sdg.ac.cn/).
In addition, Glyco-M*Grid, a grid portal-based integrated environment for e-Glycomics, provides a powerful tool for tackling the glycobiology in the avian flu systems. Preliminary equilibration and minimization steps of the MD simulations as well as virtual screening experiments are carried using PRAGMA grid. Natural compound library is screened using the NaPIMM portal (http://www.usm.my).
Education
Open Policy
Project Extranet Wiki
Participants
Principal Investigator
Peter Arzberger, Ph.D.
co-PI
Wilfred Li, Ph.D.
co-Investigators
Maqs Alam, Ph.D.
Karpjoo Jeong, Ph.D.
Jung-Hsin Lin, Ph.D.
Kai Nan, Ph.D.
Osamu Tatebe, Ph.D.
Habibah Wahab, Ph.D.
Xiaohui Wei, Ph.D.
Key Personnel
Postdoctoral Fellows & Researchers
Irene Newhouse, Ph.D.
Rommie Amaro, Ph.D.
Youngjin Choi, Ph.D.
Dong Xu, Ph.D.
Graduate Students & Programmers
Zhaohui Ding, MS
Ze Luo
Lily Cheng
Wes Goodman
Linwoo Kang
PRIME Undergraduate Students
Hsing Pao
Ryan Ferell
Advisory Committee Members
J. Andrew McCammon, Ph.D.
Art J. Olson, Ph.D.
Satoshi Sekiguchi, Ph.D.
Fang-Pang Lin, Ph.D.
Jysoo Lee, Ph.D.
Program Officers
Mary Kratz, Ph.D.
Stanley Saiki, M.D.
Institutions
Funding Agency
Telemedicine & Advanced Technology Research Center (TATRC)
The project is supported by TATRC Award W81XWH-07-2-0014, and also partially supported by respective institutions and their funding agencies through collaborative research and development activities. PRAGMA is supported by NSF grant no. INT-0314015 and OCI-0627026.
Workshops
1st TATRC Avian Flu Grid Workshop
Aug 6-9, 2007
Honolulu, Hawaii, USA
2nd TATRC Avian Flu Grid Workshop
TBA
Publications & Resources
Papers
Amaro, Rommie E., David D. L. Minh, Lily S. Cheng, William M. Lindstrom, Jr., Arthur J. Olson, Jung-Hsin Lin, Wilfred W. Li, and J. Andrew McCammon. Remarkable Loop Flexibility in Avian Influenza N1 and Its Implications for Antiviral Drug Design. J. AM. CHEM. SOC. 2007, 129, 7764-7765
Z. Ding, X. Wei, Y. Luo, D. Ma, P. W. Arzberger, and W. W. Li, "Customized Plug-in Modules in Metascheduler CSF4 for Life Sciences Applications," New Generation Computing, p. In Press, 2007.
Z. Ding, X. Wei, D. Ma, and W. W. Li, "VJM -- A Deadlock Free Resource Co-allocation Model for Cross Domain Parallel Jobs," in HPC Asia 2007, Seoul, Korea, 2007, p. In Press.
K. Jeong, J. Lee, D. Kim, Y. Choi, S. B. Lim, S. Jung, S. Hwang, D. Heo, and O.-H. Byeon, "A Grid Computing System for Collaborative Molecular Simulation," in 3rd IEEE International Conference on e-Science and Grid Computing, Dec 10-13, 2007, Bangaore, India, 2007, p. Submitted.
Y. Choi, S. Jung, D. Kim, J. Lee, K. Jeong, S. B. Lim, D. Heo, S. Hwang, and O.-H. Byeon, "Glyco-MGrid: A Collaborative Molecular Simulation Grid for e-Glycomics," in 3rd IEEE International Conference on e-Science and Grid Computing, Banglore, India, Accepted, 2007.
Posters
Abstract for PRAGMA 13 Poster Session
Related Portals
Avian Flu Info (Chinese/English)
CNIC portal for Bird Flu and related Pandemic Diseases (Chinese)
Web Conferences
Acrobat Connect Professional
Prerequisite
Basic Requirement
- Headset with microphone
- WIRED connection, do not use wireless connection
Software Requirement
System Configuration
Windows 98 SE, 2000, XP, Windows Vista™ Home Basic, Home Premium, Ultimate, Business, or Enterprise (32-bit or 64-bit editions) Internet Explorer 5.0 or higher Mozilla Firefox 1.5 Netscape Navigator 7.1 Mac OS X 10.2, 10.3, 10.4 (PPC/Intel) Safari 1.1 or higher Mozilla Firefox 1.5 Additional requirements Adobe Flash Player 8 or higher Minimum bandwidth requirement is DSL/Cable (wired connection recommended) Minimum 1 GHz processor recommended when screen sharing
- Preferred
- web camera
Setup Guide
- Windows and Mac Supported, minimum 1 GHz CPU, and a web browser
- Install Adobe Connect Plugin
- Download site
- go to the meeting URL and run Meeting ... Audio Setup Wizard ...
- if it's the first time, you should install the Adobe Connect Plug-in for your platform
- then proceed through the setup steps, the key is to choose the correct microphone
Troubleshooting
MCU Sessions 4+ parties
AIST 163.220.2.102
Calit2 137.110.147.23, Room 3004
CNIC 159.226.10.96
KISTI ?
Konkuk 203.252.151.11; 203.252.154.36
SDSC 132.249.65.243, Room 377
SDSC MCU 132.239.1.216 (call-out required)
Tsukuba U 163.220.103.5
U Hawaii 128.171.59.28 (MA); 166.122.7.221 (IN)
USM ?
JLU ?
Note:
- The Calit2 servers in room 3004, 4004, 5004, 6004 are capable of handling less than 4 parties without a web MCU session.
- Skype video beta also supports 4 parties or less.
Polycom PVX Behind a network router
- Only version 8.0.2 is confirmed to work with MCU by us. Please visit Polycom PVX site to download the update or purchase a new license. List price $149.
- Network Settings: Use Auto Detect IP address, which should be your router's network IP address
- Port Forwarding: Set up the following port forwarding services on your router
Polycom port 3230 -3237 (TCP/UDP) PolyH323 port 1720 (TCP) PolyT120 port 1503 (TCP) PolySIPU port 5060 (UDP) PolySIPD port 5060 (TCP)
These services should be forwarded to your internal IP address assigned by your router: typically 192.168.0.? or 10.1.1.?. Note: Use the "Address Reservation" feature of your router to prevent having to set the internal IP address yourself due to changes in DHCP server IP assignment
- Test your connection
Note:
- If you are only getting voice, or fail to connect, or your connection crashes, try
- dropping the default call rate to 96 kbps in the Network Bandwidth panel
- Try either the call-in or call-out feature from the MCU
- Always use a wired connection for best possible experience.
Related Links
Conferences and Workshops
Anti-influenza conference, June 2007
Options for Control of Influenza VI, June 2007
Bangkok International Conference on Avian Flu January 2008
World Summit on Antivirals, July 2008
Web sites
Options for the Control of Influenza VI
