AHM 2005 e-Malaria University of Southampton 1 Jeremy Frey
E-Malaria
AHM 2005Jeremy Frey
School of ChemistryUniversity of Southampton
AHM 2005 e-Malaria University of Southampton 2 Jeremy Frey
Malaria
Malaria kills over 2 million annually Caused by a parasite and
transmitted by mosquitoes Resistance to existing drugs is
growing New drugs are needed Computational modeling can speed
up process and save laboratory time and costs
AHM 2005 e-Malaria University of Southampton 3 Jeremy Frey
Why target school pupils?
Numbers of pupils choosing science courses are falling
Science is perceived as boring, hard and irrelevant to peoples lives
Decline is numbers is worrying for the science community and society at large
AHM 2005 e-Malaria University of Southampton 4 Jeremy Frey
What difference can the e-Malaria project make?
Example of chemistry in context Authentic activity Chance drug candidates could go
on for in vitro & in vivo tests
AHM 2005 e-Malaria University of Southampton 5 Jeremy Frey
What does the project provide? Range of supporting texts and links Interactive quizzes Forum Links with university departments Support from project team Drug design tools
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Resource design Based on feedback
from range of project supporters
Designed to look contemporary and interesting
Accessibility for students with SEN (Special Educational Needs)
Interactivity for interest
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Interactivity
Core to keeping students involved
Increases the amount learnt, understood and memorized by students
Provides interest
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Supporting Material
Intermolecular forces Drug design Proteins and amino acids Enzymes
AHM 2005 e-Malaria University of Southampton 9 Jeremy Frey
Design
Take a suitable enzyme target in the malaria parasite
Design small molecule as possible drug
‘Dock’ in to enzyme target to find improved binding
Modify to yield drug like molecule
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The Target - DHFR Regulates part of
DNA synthesis Present in both
humans and parasites
Different regulation methods between humans and parasites make it an excellent target
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Possible target - block an enzyme that decodes DNA - DHFR
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Design a possible drug
Now have to find the molecule’s real 3D shape
Use quantum mechanics program to work out the molecule’s shape
AHM 2005 e-Malaria University of Southampton 13 Jeremy Frey
3D shape
Now try to dock the drug in to the enzyme active site- but which way round? Lots of ways to try!
How well does it bind?
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System Outline
Distributed computing cycle steeling grid
AHM 2005 e-Malaria University of Southampton 15 Jeremy Frey
Why UD UD software is relatively heavy
weight but highly secure Need to be secure to allow us to run
the GOLD software This is real and valuable software
which must be protected. Don’t have to worry about invalid
answers as we can always readily check
AHM 2005 e-Malaria University of Southampton 16 Jeremy Frey
AHM 2005 e-Malaria University of Southampton 17 Jeremy Frey
AHM 2005 e-Malaria University of Southampton 18 Jeremy Frey
Molecular Structure File Format Conversion
Convert to middleware model
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Web Server
Workflow
Docking
3D
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Current drug Trimethoprim, score 57.49
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Organo-phosphorous
Score 68.1 Yes but what else
does it bind to – a bit like a nerve gas?
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Peptides as drugs?
Ala-ala-ala (tripeptide)
score 50.15 Suitable as a
drug?
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Docked conformation of Glu-Phe-Ala, score 68.88 surprisingly large value!
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Groups 16
Sites 5
Users 85
Molecules 692
AverageMinimisation Time
9 seconds
Average Docking Time 5 minutes 20 seconds
Statistics
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Issues Instructions to users Competition in the schools
Need to provide personal, school and overall summaries
Keeping the systems running Robust web server & software Differences between browsers! Log file overload Network problems
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Why do it? Chance to see what research (or
industry) is like Increase confidence Do things you wouldn’t have a chance to
do normally Can give valuable experience which puts
you ahead of competition at interviews Can be tailored to suit career dreams
AHM 2005 e-Malaria University of Southampton 27 Jeremy Frey
Related projects Related to other seti@Home projects
Graham Richards drug screen Climate prediction
But student designs molecules not just supply computer power to screen someone else’s choice of a possible drug
Student sees and plays with input & output
More complex exchanges between us and the students, but data volumes not large, but frequent
AHM 2005 e-Malaria University of Southampton 28 Jeremy Frey
E-MalariaUse Chemistry + e-Science to allow students to search for anti-malarial drugs.Makes use of real industrial strength programs to check if your idea for a drug might work.Uses spare computer power to do the calculations
AHM 2005 e-Malaria University of Southampton 29 Jeremy Frey
People & Organizations Rob Gledhill Sarah Kent Andrew Milstead Brian Hudson John Metcalfe John Frampton Havant College
Jon Essex Graham Richards CCDC UD JISC EPSRC