Arbeitsgruppe Prof. Dr. G. Klebe

Relibase provides two different ways of retrieving protein and ligand data: SMILES and MolEd

---

SMILES search

In principle the SMILES search option enables substructure based ligand search in Relibase. By using SMILES you are able to describe chemical structures by a character string. Further details can be found at daylight inc. For example let's search for benzamidine by typing the SMILES code of this structure into the frame named Enter SMILES Code.

      NC(=N)c1ccccc1
  

and press Submit.

A new window appears presenting the query results.

2D/3D Search by using MolEd

Sketch the desired structure by 2D/3D substructure searching: MolEd The 2D/3D button in the menu bar takes you to the chemical query drawer MolEd. This allows you to draw search queries for ligands or for protein-ligand interactions.

Drawing a query

To draw benzamidine as a chemical fragment, select the Draw mode and use the left mouse button to draw the fragment. Predefined fragments (e.g. a 6-membered aromatic ring) can be selected from the Group popup menu. Select the 6-membered aromatic ring from the Group menu. The element and bond types can be selected from two popup menus at the top. Special element types are:

• ? any atom.
• R any atom, except hydrogen.
• X any atom, except hydrogen and carbon.

To change atom and bond types, select the Change mode and click on atoms and bonds to change their types to the selected type.

Selecting atoms

There are two ways to select a set of atoms:

1. select the Select mode and select (or deselect) the atoms using the left mouse button;
2. In any mode, you can select (or deselect) atoms using the middle mouse button.

You can deselect all atoms using the Deselect All button.
Make sure ligand atoms colored in black, protein atoms in blue, respectively.

Moving atoms

Using the right mouse button, in any mode, to move the selected atoms.

Deleting atoms

There are two ways to delete atoms:

1. select the Delete mode and delete atoms using the left mouse button;
2. select the atoms you want to delete (see above) and hit the Delete Selected button. You can delete all atoms by hitting Delete All.

Ligand substructure searching

To search for fragments within ligands, first define your query as described above, making sure all atoms in the fragment are connected (i.e. the query should be one fragment). If you want to inspect the superimposed hits visually (not recommended if the search is likely to result in a large number, 100, of hits), select the atoms you want to superimpose, before you start the search. At the moment, Relibase can only use three atoms for this superposition; if you select more, it will only use the first three. Next hit the Submit to Relibase button to start the search.

The query results window appears as already seen in the SMILES procedure. Aktivate the button Superimpose hits on selected atoms.

Evaluating the results

To view the query results in 3D you have to launch RasMol via the 3D Viewer in the 3D Visualizer Toolbox. In the Rasmol window the first hit is shown. If the superimposition has been enabled an option Visualization is offered in the lower left corner of the query results window. Clicking this button will show the superimposed ligand-structures in RasMol.

Combining Hitlists

You have the possibility to save the query results in a Hitlist by typing the desired name of the Hitlist in the Save in Hitlist box. Relibase always presents two browser windows, go back to the general query form window and press the Hitlists Button.
Using at least two Hitlists you are able to combine Hitlists by boolean operators (AND, OR, NOR). In the following example a search for a ligand containing a sulfonamide group, a benzamidine structure but no fluoride.

1. Sketch a sulfonamide structure by using MolEd or the SMILES-Code

   SMILES: CS(=O)(=O)N 

   and save the query as sulfo.
   
   
2. Use the same procedure to create a Hitlist for the benzamidine structure

   SMILES: NC(=N)c1ccccc1 

   and save the query as benz.
   
   
3. Create a third Hitlist containing all ligands with a carbonbound fluoride

   SMILES: CF

   and save as fluoro.

Click the Hitlist button to obtain the query results.

Select the ligand set BENZ as ligand set 1 and SULFO as ligand set 2 choose AND as the boolean operator in the Combine Ligand Sets frame. Name the new ligand set as BENZ_SULFO and submit the query. A new ligand set named benz_sulfo, containing all ligands with a sulfonamide and a benzamidine structure is returned. To show the ligands found click at BENZ_SULFO in the ligand set list.

In the next step use the boolean operator NOR to exclude FLUORO from the ligand set BENZ_SULFO and submit.

---

top of the page