Download Catalyst

TM
Catalyst
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What is CatalystTM ?
Structural databases
Designing structural databases
Generating conformational models
Building multi-conformer databases
Database searching and structure
mapping
Hypothesis
• A critical task in drug discovery is
building a model of the characteristics of
the drug you are trying to develop.
• In CatalystTM this model is called an
hypothesis.
• The hypothesis is a set of
characteristics that distinguishes a
group of molecules.
Hypothesis: What does it
represent?
• If you have a set of compounds that
have been assayed for a particular
biological activity, CatalystTM will
generate an hypothesis that represents
the activity of these compounds.
What does this mean?
• If you are looking for a refined ACE
inhibitor and you have the structures
and activities of 20 compounds that
exhibit inhibition to ACE, CatalystTM will
generate an hypothesis that represents
the structure-activity relationships of the
20 compounds and correlates their
structures with ACE inhibition.
What data is contained in the
hypothesis?
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3D data
2D data (topological data)
1D parameters
Constraint descriptors
Chemical functionality data.
What data is contained in the
hypothesis?
• The hypothesis is built to contain an
assembly of substructures and chemical
functions locate at specific positions in space.
• Variation in the substructure at specific
positions may be included in the hypothesis
e.g. the substructure might contain a phenyl
ring with either N, O or F at position 4.
The chemical structure
hypothesis?
The chemical functions
hypothesis.
Using the hypothesis to search
the database?
Compound 1
Compound 2
Compound 3
Compound 4
Compound 5
Comparing the molecule to the
hypothesis?
Using the hypothesis to estimate the
activity of compounds? The hypothesis.
Using the hypothesis to estimate the activity of
compounds? The hypothesis and the molecule.
Using the hypothesis to estimate the activity of
compounds? The hypothesis and the molecule fit.
Using the hypothesis to estimate the activity of
compounds? The hypothesis and the molecule.
Using the hypothesis to estimate the activity of
compounds? The hypothesis and the molecule fit.
Using the hypothesis to estimate the activity of
compounds? The molecules.
Summary
• What is an hypothesis and how is it
used in drug discovery?
• How do you search a database with an
hypothesis?
• Fitting a compound to an hypothesis?
• Estimating the activity of a compound
from the hypothesis?