AnchorQuery leverages the concept of anchors, amino acid residues that bury a large amount of solvent accessible surface area at the protein-protein interface. Every compound in our multi-component reaction (MCR) accessible virtual library contains an anchor analog, a functional group that is a chemical mimic of a specific amino acid. AnchorQuery pharmacophore queries always include an anchor feature in addition to the standard hydrophobic, ionic, and hydrogen bond donors. All non-anchor features are stored relative to a coordinate system defined by the anchor in an efficient spatial index. Pharmacophore searches scale relative to the breadth and complexity of the query, not the size of the database. As a result, full 3D pharmacophore searches can be executed over billions of explicit conformations in a matter of seconds.
A video overview of using AnchorQuery is recommended for new users. After watching the video, consider loading some of the provided examples and familiarize with the AnchorQuery interface using an already generated pharmacophore.
The general workflow of using AnchorQuery when targeting a new PPI is:
- Isolate the key interacting residues of an interaction (including at least one anchor - Trp,Phe, or Tyr - residue). The ANCHOR database can be used to quickly identify these residues. Store the residues into their own file (sdf, mol, or pdb).
- Isolate the receptor of the interaction (optional) into its own file (pdb preferred).
- Load the interacting residues (Load Residues) and identify and disable unimportant pharmacophore features.
- Load the receptor (Load Receptor) and identify and disable uninteresting receptor-based features (optional).
- Search. As easy as clicking a button (Submit Query).
- Iteratively refine. Adjust the search parameters until the desired number and quality of compounds is achieved.
- Download the results for secondary screening.