Abstract: Heterogeneous compound databases can be searched for compounds which are likely to have the same biological activity as a known (query) molecule. Query molecules and the molecules in the database are split into fragments according to common fragmentation rules. Fragments are aligned in a uniform conformation according to a topomeric alignment process and interaction energy fields, typically steric fields, between a probe and the fragment atoms are generated to capture the fragment shapes. Comparison of the fields for the query fragments with the fields for the database compound fragments yields a measure of shape similarity. Searches for similarly shaped substructures and cores can also be readily accomplished. Pharmacophoric style features can be defined for the topomerically aligned fragments but with user specified weighting of the importance of each. Differences in features are defined with the same dimensionality as shape so that both shape and features can be used to search.

Abstract: The static and electrostatic interaction energy fields between probe atoms and the atoms of a topomerically aligned fragment placed in a three-dimensional grid may be used to derive a CoMFA model. The topomeric CoMFA model coefficients may be used to predict partial activity values for fragments not derived from molecules of the activity series. The partial activities can be summed to provide a predicted activity for all fragment positions of the activity series molecules. A Virtual Library in which topomerically aligned fragments are associated with their respective steric and electrostatic interaction energies can be searched for fragments similar in shape to the fragments derived from the molecules of the activity series. The identified fragments can be used with the topomeric CoMFA coefficients to predict their activity if used in the molecular activity series.

Abstract: Heterogeneous compound databases can be searched for compounds which are likely to have the same biological activity as a known (query) molecule. Query molecules and the molecules in the database are split into fragments according to common fragmentation rules. Fragments are aligned in a uniform conformation according to a topomeric alignment process and interaction energy fields, typically steric fields, between a probe and the fragment atoms are generated to capture the fragment shapes. Comparison of the fields for the query fragments with the fields for the database compound fragments yields a measure of shape similarity. Searches for similarly shaped substructures and cores can also be readily accomplished. Pharmacophoric 10i;.: style features can be defined for the topomerically aligned fragments but with user specified weighting of the importance of each. Differences in features are defined with the same dimensionality as shape so that both shape and features can be used to search.