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synopsis

The SuperSite is an encyclopedia that is dedicated to a ligand and binding site oriented view of the protein structural space. SuperSite integrates evolutionary information in the proteins as well as predicted binding sites from LigsiteCSC. A point set match algorithm is implemented that allows to screen the surface of a protein for the occurrence of possible binding sites as well as a similarity screen for similar compounds based on fingerprints.

Tasks related to the SuperSite

• Discovering the ligand space of the PDB via certain criteria. [link]
• Check for evolutionary conservation of residues using HSSP files. [link]
• Display possible binding sites of proteins via the LigsiteCSC algorithm. [link]
• Similarity screen for ligands contained in the SuperSite (use eg this drug file). [link]
• Screening a protein for the possible similarity of binding pockets towards certain known drug binding sites.[link]

For more information check out our documentation.

Last update: 25.06.2009

Where to start

Case Study 1: Spatial mining

When it comes to the elucidation of the binding between small compound and protein it is of special interest what common features of all binding sites of known binding sites might be. In the case of Vitamin B6 there are more than 100 protein binding sites available for inspection. An investigation reveals, that amino acids like glycine and others seem to be conserved at specific spatial positions.

• Step 1: Click on "Drug Encyclopedia" in the menu left.
• Step 2: Enter PLP as Het-ID in the first form.
• Step 3: Select "Show all binding sites and ligand conformations".
• Step 4: Select protein pockets "1bjo, 1c7n and 1dje".
• Step 5: To highlight interesting residues like glycine and histidine simply apply the following script: "select *; color grey; select gly; color red; select lys; color blue; select his; color green; select plp; color cpk;"

You can see for instance that the red spheres (glycine) are concentrated in a spatial area.

Case study 2: Determination of binding pockets

For the elucidation of possible function of a protein it is of interest where to find possible binding pockets. For further inspections we also provide insight into the conservation of residues of proteins.

• Step 1: Click on "Search protein" in the menu left.
• Step 2: Enter "1wdp" as PDB ID.
• Step 3: Select "Cartoon", "Show" button in section HSSP conservation and the first pocket in LigSiteCSC predictions.

You can see a certain conservation in the residues (in red) as well as the prediction of the binding site (green) what points to a possible binding pocket. Check out protein with PDB-ID 1b1y for a nice confirmation.

Case study 3: Ligand Similarity Screening

Following the SAR paradigm this enables to hypothesize about a similar method of action for similar compounds. If these compounds are similar enough in overall shape a proposition of novel binding partners through this approach is possible.

• Step 1: Download this compound - Methotrexate.
• Step 2: Click on "Ligand similarity screening" in the menu left.
• Step 3: Upload compound (File => Open) and issue similarity screening (button at the bottom).
• Step 4: Pick first ligand with ligand "FOL" (eg. PDB-ID: 1RA7).

It is known that MTX replaces FOL in the folic acid biosynthesis, what is exactly what this finding shows.

Please cite

Bauer R. A., Günther S., Heeger C., Jansen D., Thaben P. and Preissner R.
SuperSite: Dictionary of metabolite and drug binding sites in proteins.
Nucleic Acids Res. (2008)