Why doesn't Phase find any hypotheses when it looks like there is an obvious ligand alignment?

The most frequent reason why a common pharmacophore isn't found is because one or more of the expected common features is a hydrophobe, and the hydrophobe has too small an accessible surface area in one or more of the actives. For example, the hydrophobe might be in a rigid part of the structure and be buried in every conformer. Sites that are not surface-accessible are excluded from the search for common pharmacophores. From Suite 2007 Update 1 on, you can adjust the threshold for the accessible surface area in the SAS Options dialog box, which you open from the Edit Features panel.

You can check for surface accessibility by importing one of the structures into the Hypothesis Table workflow, and attempting to create a hypothesis from the structure. Only surface-accessible features are displayed.

Back to Search Results