Virtual discovery for the real world
Joe Mernagh
19 May 2005
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15 Years Cap Gemini
• Consultant: knowledge systems, IT strategy, Life Sciences R&D
• Senior Manager Life Sciences Global Management Unit
4 years Evotec OAI
• Chief Knowledge Officer
• Executive manager responsible for Knowledge Management and IT
• Innovative drug discovery solutions
Active Dynamics
• Independent consultant and interim manager
• Focus on companies involved in drug discovery
• Projects with potential for long term value creation
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Laboratory based discovery
•
Expensive
•
Long setup stage, slow experiments
•
Compounds and assays degrade
•
Laboratory infrastructure
•
Chemistry space is defined by access to physical compounds
Virtual discovery
•
Cheap
•
Immediate, rapid experiments
•
No shelf-life or repeatability issues
•
No physical infrastructure
•
Coverage of all accessible chemistry space
Virtual discovery, both rational and high throughput, is playing an ever greater role in the discovery process
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• Genomics and proteomics research has given the world a wealth of potential druggable targets to work on and has started a race to identify appropriate small molecules
• High throughput laboratory chemistry and screening technologies have not been powerful enough to deal with the avalanche of targets
• There is no appetite to scale up physical chemistry and screening beyond current technology limitations
Only virtual techniques, discovering highly profiled candidate molecules for laboratory testing, can address the bottleneck
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• The complexity of virtual discovery technology is a major constraint for SMEs - there is an opportunity to provide a complete ASP service for discovery informatics
• Processing requirements for virtual discovery are potentially very large and very irregular – an on-demand facility combining leading edge software and large scale computing power might be highly attractive proposition for companies of all sizes
• The combination of unique virtual discovery technology and massive computing power will create wholly new ways of exploring chemical space
In virtual discovery, the only constraints are the quality of the algorithms and the availability of processing power
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The idea is to allow researchers to buy virtual drug discovery capability on an as-needed basis by plugging their workstations into the internet
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Java GUI Web Services Access
ChemAxon Discovery Tools
Virtual Compound Space
Virtual Synthesis Engine ChemAxon Reaction Library
Large Scale Computing Facility
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Create me a new virtual library from my selected reactions and inputs
Synthesise
New Virtual
Compounds
How chemically diverse are my selected compounds ?
Diversity and
Cluster Analysis
Java GUI
Find
Chemical
Route
Give me a synthetic route and reagents for my selected compounds
Find compounds and scaffolds to fit a specific bioavailability and physico-chemical profile
Web Services Access
Identify
Drug-like
Candidates
ChemAxon Discovery Tools
Virtual Compound Space
Virtual Synthesis
Engine
ChemAxon Reaction
Library
Large Scale Computing Facility
Profile
Compounds
What is the pKa,
LogD, LogP, polar surface area etc of my compounds ?
Screen selected compounds for efficacy, ADME and toxicity
Screen
Compounds
Design De-novo
Compounds
Design
Analogs
Fragment based rational design of de-novo compounds
Input compound create new, synthetically feasible analogs
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High performance fingerprint and graph based topology searching
Chemical and pharmacophore similarity searching
Optimised high throughput virtual screening
Powerful java based structure, reaction and query editor
Chemical terms =
Smart Reactions = synthetically feasible products
Library of key preparative reactions
Profile compounds: elemental analysis, pKa, LogP, LogD, polar surface area, charge distribution, refractivity, major microspecies etc
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At this User Group Meeting, you can participate :
• Discussion about the composition and value of an on-demand virtual discovery centre
• Survey of market interest in such a facility
… or back of envelope design over a beer !
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As a partner, you can participate in an exciting new business proposition which already has the interest of a leading global provider of information technology services :
• Help us develop the GUI environment which will provide the entry point to the virtual discovery tools
• Hook in your virtual screening technology (target based virtual screening, ADME/T models etc)
• Be an early adopter and get an opportunity to contribute your particular requirements during the design process
There is a real commercial opportunity to be part of a unique, ground-breaking project
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