catalyst tm what is catalyst tm ? structural databases designing structural databases generating...
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CatalystTM
• What is CatalystTM ?
• Structural databases
• Designing structural databases
• Generating conformational models
• Building multi-conformer databases
• Database searching and structure mapping
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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.
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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.
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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.
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What data is contained in the hypothesis?
• 3D data
• 2D data (topological data)
• 1D parameters
• Constraint descriptors
• Chemical functionality data.
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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.
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The chemical structure hypothesis?
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The chemical functions hypothesis.
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Using the hypothesis to search the database?
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Compound 1
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Compound 2
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Compound 3
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Compound 4
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Compound 5
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Comparing the molecule to the hypothesis?
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Using the hypothesis to estimate the activity of compounds? The hypothesis.
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Using the hypothesis to estimate the activity of compounds? The hypothesis and the molecule.
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Using the hypothesis to estimate the activity of compounds? The hypothesis and the molecule fit.
![Page 19: Catalyst TM What is Catalyst TM ? Structural databases Designing structural databases Generating conformational models Building multi-conformer databases](https://reader035.vdocuments.site/reader035/viewer/2022062423/5697c02d1a28abf838cd9ca3/html5/thumbnails/19.jpg)
Using the hypothesis to estimate the activity of compounds? The hypothesis and the molecule.
![Page 20: Catalyst TM What is Catalyst TM ? Structural databases Designing structural databases Generating conformational models Building multi-conformer databases](https://reader035.vdocuments.site/reader035/viewer/2022062423/5697c02d1a28abf838cd9ca3/html5/thumbnails/20.jpg)
Using the hypothesis to estimate the activity of compounds? The hypothesis and the molecule fit.
![Page 21: Catalyst TM What is Catalyst TM ? Structural databases Designing structural databases Generating conformational models Building multi-conformer databases](https://reader035.vdocuments.site/reader035/viewer/2022062423/5697c02d1a28abf838cd9ca3/html5/thumbnails/21.jpg)
Using the hypothesis to estimate the activity of compounds? The molecules.
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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?