Usage instructions

1. Specify the input

Using ChemProt-2.0, you will have the possibility to perform five different searches:

1. by bioactive chemicals
2. by proteins
3. by human diseases
4. by adverse drug reactions and
5. by Anatonomical Therapeutic Chemical classification (ATC code)

using names, identifiers, keywords and structural queries for compounds.

1a. Search by bioactive compound:

There are 5 possible ways of entering molecular structure information in ChemProt.

1. Draw the molecule in the JME window to the right and click on the "Import" button to translate to SMILES
2. Insert the SMILES strings of the molecules in the middle window
3. Submit a SMILES strings from a file (*.smi). Note that the file should contains only one SMILES
4. Read the structures from a sdf file. Note that the file should only contain one sdf input (*.sdf) Sample copy
5. Type the name of a compound in the "Type compound name" field. Various chemical names and synonymous can be used and are displayed dynamically

The SMILES entry window and the smi file should have preferably the canonical smile format. Hydrogens will not be considered for the similarity search.

Structural similarity search:

The chemical search is based on the assumption that chemicals sharing similar structure also share similar activity to a given protein.

To do the structural similarity search 2 types of fingerprints can be used:

1. MACCs fingerprints (composed of 166 queries; atoms- or fragment-based)
2. FP2 fingerprints (path-based fingerprint of length from 1-7 atoms computed from OpenBabel)

The structural similarity between two chemicals is measured using the tanimoto coefficient (Tc). The closer to 1, the higher the similarity.
To limit the size of the output, chemicals with a Tanimoto coefficient Tc > 0.85 for MACCs and > 0.60 for FP2 are shown by default. The user is free to modify the Tc threshold, between 0.8 and 1 for MACCs and between 0.5 and 1 for FP2.

1b. Search by protein name (target name):

Type a name of a protein in the "Search by Target name" field. Protein names and UniProt (http://www.uniprot.org/) identifiers are recognized terms in ChemProt. For example, "5-HTT", "serotonin transporter" or "P31645" can be used to define the Sodium-dependent serotonin transporter.
Then click on submit and all compounds with bioactivities on this target will be depicted.

The user has the option to select "include similar proteins (BLAST)". By doing so, similar proteins (based on the protein sequence) and bioactive compounds associated to them will be shown. A -log(E-value) of 10 is used as a default (corresponding to a BLAST E-value of 10^-10) but the user can specify the threshold.

1c. Search by human disease name:

Type a disease name in the "Search by disease" field and press "Submit". Proteins and bioactive compounds associated to them will be shown. The disease ontology used in ChemProt is based from the diseasome study (http://diseasome.eu/).

1d. Search by side effects:

Type a side effect name in the "Search by Side effect" field. You can enter any side effect name supported by DailyMed. Press "Submit" and proteins and bioactive compounds associated to them will be shown.

1e. Search by ATC code:

Type am ATC code in the "Search by ATC code" field. The search can be done at different level following the categorization schema defined by the World Health Organisation (WHO).

2. Select Databases

Chemical-Protein information has been gathered from different databases. You can decide if you prefer to get the data from all the databases in one layout (select "Check all") or if you prefer to use specific databases.

3. Submit the job

Click on the "Submit" button. The status of your job (either 'queued' or 'running') will be displayed and constantly updated until it terminates and the server output appears in the browser window. It is estimated around 30 sec. to 45 sec. is needed to get an output per molecule.

4. Toggle between the various functionalities of ChemProt

Go to the output tab on the top of this page and learn about the many different functionalities in ChemProt or click here

At any time during the wait you may enter your e-mail address and simply leave the window. Your job will continue; you will be notified by e-mail when it has terminated. The e-mail message will contain the last part of the URL under which the results are stored; you will have to add in front the path: www.cbs.dtu.dk/ to get directly to the heatmap output.
For example: www.cbs.dtu.dk/cgi-bin/webface?jobid=chemprot,508A854007F7BBBC
they will remain on the server for 24 hours for you to collect them.