Citation

SimiCon: A web tool for protein-ligand model comparison through calculation of equivalent atomic contacts. Manuel Rueda, Vsevolod Katritch, Eugene Raush and Ruben Abagyan. Bioinformatics (2010) 26(21): 2784-2785 (link).

Description

SimiCon is web server that identifies equivalent atomic contacts between two protein-ligand complexes. The results are presented in form of plain text, HTML, tables and 3D interactive molecular objects.

Input Form

Reference and target complexes can be uploaded as PDB coordinate files, or retrieved by using PDB IDs.

The server is optimized for parsing proteins as receptors and chemical compounds as ligands (HETATMs). Missing heavy-atoms from incomplete amino acids will be added by Molsoft's ICM program. Note that chains containing TER signals (i.e., those coming from some modeling packages) will be split into different chains

In "Upload mode", only the first protein chain and the first HETATM molecule will be analyzed. If you want to include a "multi-chain" receptor in a single run, please join the chains manually so that they become a single one. The server allows to compare two complexes having receptors with non-identical protein sequences, however, only aligned amino acids will be analyzed. As an extra feauture, the server also allows comparing complexes containing different ligands. Atoms in both ligands are mapped according to ICM's maximal common chemical substructure method.

For most PDB complexes containing small molecules the calculation time is ~ 2 seconds for the standard 4 Å cutoff, and up to ~ 20 seconds when the largest (12 Å) cutoff is used. The CPU time will be increased (see required times) when the ligand presents symmetry groups displaying large symmetry numbers (e.g., ≥ 4 ).

An error message will be displayed when any of the selections present errors. Some PDB IDs may give issues because of their "unconventional" nomenclature. If you are in trouble, please try with the upload mode after manual parsing (e.g., erasing unwanted molecules, renaming HETATMs, etc.) of the files.

Results Page

The results are first presented as text, and as a HTML table consisting of three columns; the ligand atoms mapping, the reference protein contacts (RC) with their distances, and the target protein contacts (TC) with their distances. The equivalent contacts (EC) between the reference and the target are displayed with the same colouring scheme. These lists are used to calculate some general metrics, such as the coverage = EC/RC and the accuracy = EC/TC (see image below). Note that, in order to be considered as equivalent, two contacts must have a mapped ligand atom (see above).

If one of the atoms of the target is symmetric with respect to other in the reference the distance will be shown as (S:x.xx)

2yxu.a/^L263/cd1 (3.96)

2yxu_1.b/^L263/cd2 (S:3.76)


For a full experience we recommend switching to the 3D interactive version by clicking "View Results with Active ICM" button. If so, all the cells on the HTML table become clickable and the distances are displayed online via activeICM/ active X plugin (see image below). The color scheme goes as follows: Reference protein, reference ligand, target protein and target ligand. Note that the proteins are superimposed to facilitate structural comparison.

The embeded ICM object used by ActiveICM can be also downloaded as a single file that can be viewed locally with the ICM browser. Both are freely available for the public (see download links at the end of this page).

The contacts for the reference, the target and their intersection can be downloaded as a comma separated value (.csv) file, compatible and supported by almost all spreadsheets and database management systems. The user can re-process the contact lists according to his/her needs.
The results are stored 1 month.

Submitting Multiple Jobs from the command-line

Apart from a standalone calculation, we envision that some users may wish to use the command-line to execute the CGI with multiple targets. We are providing an example Perl script implemented using the LWP library (installed by default in most Linux distributions and Mac OS) that will avoid the necessity for "screen scraping" of HTML. The command-line results will be also stored and accessible through a web browser at http:/wwww-ablab.ucsd.edu/SimiCon/data/idJob, where idJob is the identification number of the job.
The user must replace the input parameters inside the script according to the naming of the files to compare. The example script can be executed in a Linux shell by typing:
perl ./SimiConLWP.pl
For multiple submissions, the replacement can be done from an external Linux shell script, or by adding a loop inside the Perl script. Please read the instructions inside the Perl LWP script.

If you have any specific question, or found a bug, please contact the author at mrueda@scripps.edu.

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