catalyst tm what is catalyst tm ? structural databases designing structural databases generating...

CatalystTM

• 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?

• 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?