Interaction Search finds structures whose ligand makes the same 3D pattern of interactions with its receptor as your query, for example a halogen bond and an aromatic contact at a given angle. It looks across all structures and ligands, so it can find different scaffolds with a similar binding mode. Hits are superposed on the query.
A fuzzy search can take tens of minutes. Start with a precise query, then loosen it if you get too few hits.
The Interaction Search dialog opens with the selected contacts.
Structure shows the structure the contacts come from. Under Interactions, each contact is one line of the query:
| Part | Description |
|---|---|
| Receptor | The receptor interactant type, for example Xbond acceptor, and the atom, for example 9y60-A-234 PRO:O. |
| Interaction | The interaction type, for example Halogen Bond, with the allowed distance and orientation fuzziness. |
| Ligand | The ligand interactant type (default Any) and the atom. |
| X | Removes the contact from the query. |
| Chevron | Shows the settings of the contact. |
Settings of a contact:
| Setting | Description |
|---|---|
| Receptor, Ligand | The interactant type the hit atom must have. |
| Interaction | The interaction type. Any + a group, for example Any Polar, matches every type of the group. |
| Distance in Å | Range of the interaction length. Filled in from the query contact, for example 3.4 to 5.4 Å. |
| Orientation deviation in ° | How much the direction of the contact may differ. |
| Reset parameters | Goes back to the values from the query contact. |
| Parameter | Default | Description |
|---|---|---|
| Output Name | Structure and residues, for example "9y60 P234,Y233" | Name of the result collection. |
| Filtering Mode | Chemical Diversity | Chemical Diversity: one hit per ligand, the best-scoring one. Biomol Diversity: one hit per receptor protein. Display All Hits: no filtering. |
| Maximum number of hits | 200 | Keeps only the best-scoring hits. Limits the time of fuzzy searches. |
Turn on Expert settings to show:
| Setting | Default | Description |
|---|---|---|
| Filter by Protein Family | – | Include only these families, or exclude them. |
| Filter out query molecule | Off | Leaves out hits with the same molecule as the query. |
| Filter out query structure | On | Leaves the query structure out of the results. |
| Filter out ligands binding to reference biomolecule | On | Leaves out hits that bind the same protein as the query. |
| Receptor position fuzziness in Å | 1 | How much the distance between receptor atoms of two contacts may differ from the query. |
| Ligand position fuzziness in Å | 1 | How much the distance between ligand atoms of two contacts may differ from the query. |
Known issue: Filter out query molecule, Filter out query structure and Filter out ligands binding to reference biomolecule are always applied, even when you turn them off.
Click Search to start.
A hit must match every contact of the query; partial matches are not returned. For each contact, the hit must have:
Each pair of contacts must also have the same geometry as in the query:
For example, two H-bonds at 22° match a query of two H-bonds at 8° with fuzziness 10° and 20°: the difference, 14°, is below 20°.
After superposition on the matching atoms, the score is 1 − RMSD of the ligand and receptor atoms involved in the matching contacts.
The results appear as a new collection in the Workspace, tagged Interaction Search. While the search runs, the collection shows its progress, the number of results and the elapsed time.
| Element | Description |
|---|---|
| Score | Hits are sorted by score, highest first. |
| Eye icon | Shows the hit superposed on the query, using the matching contacts only. |
| Ligands tab | One card per hit ligand, with its score, target and ligand ID. |
The collection's ⋮ menu has Add all to project, Download collection, Copy URL and Remove collection.