LiSiCA Plugin

LiSiCA PyMOL Plugin (latest update Jun/13/2021)

• LiSiCA plugin v1.1.2 for PyMOL: lisica.py
• Whole package (see Manual Installation): lisica-plugin.zip

Example Input Files

• Reference molecule: reference.mol2
• Target molecules: database.mol2

Versions and Release Notes

1.1.2

• Fixed bugs: plugin size, sorting of hits by rank, other GUI changes
• Works on Linux (tested on Ubuntu 20.04) and Windows (tested on Windows 10)
• Known issue: in PyMOL 2.5.0 the visual alignment of hits is not that nice, but results are identical as in other versions of PyMOL.

1.1.1

• The plugin has been rewritten in Python 3 using Qt5 GUI
• Works with the new PyMol 2.3 and above
• This version is still available here: lisica-plugin-v111.zip (see Manual Installation)

1.0.2

• This version works for older PyMols (versions 1.x), it is still available here: lisica-plugin-v102.zip (see Manual Installation)
• Reading of gzipped files (.mol2.gz) for target molecules
• Works without internet connection
• Background color stays as set by the user

Automatic Installation

1. Download lisica.py file.
2. Open PyMOL and go to Plugin → Plugin Manager.
3. Select Install New Plugin category and click on the Choose file... button.
4. Add the lisica.py file. In the select plugin directory window select directory and click OK
5. Close the Plugin Manager window. LiSiCA plugin should appear under Plugin → LiSiCA
6. When LiSiCA plugin is started for the first time it downloads additional required files from our server. Be patient, this may take a while.

Manual Installation (optional)

If automatic installation fails for any reason (for instance our server might be unavailable), manual installation can be accomplished like this:

1. Download lisica-plugin.zip file, which contains the entire package.
2. Extract it and find within the ".lisicagui" directory (the dot in front of the name means it is a hidden directory).
3. Copy .lisicagui directory to your home directory.
4. Install the lisica.py (see above Automatic Installation)

Input Tabs

1. Input molecules
   
   Both the reference and the target compound files need to be in the Tripos mol2 format. The reference file should contain only one (reference) compound; the target file may contain many compounds. If the reference file contains more than one compound, the first molecule is used as a reference. The molecules in the target file having the same name are considered as different conformers of the same molecule. By default only the best-scoring (by Tanimoto coefficient) conformer will be shown in the final output for the 3D screening option.
   
   In the mol2 input files, the name of the molecule (ZINC ID) must be specified under the line for the "@MOLECULE" tag. For example:

    
   @MOLECULE
   ZINC73655097
   46    48     0     0     0
   SMALL
   USER_CHARGES
   
    @ATOM
   ...
   			

   LiSiCA checks similarities based on the mol2 atom types. Hence SYBYL atom types have to be specified in the mol2 files. For example, under the @ATOM tag, each atom specification should include the SYBYL atom type, as in:

    
   1 C1         -0.0647    1.4496   -0.0592   C.3      1 <0>        -0.167
   				

   In the above line from a mol2 file, the SYBYL atom type is specified in bold in column 5.
2. Product graph dimensions
   
   In 2D screening, the option Maximum Allowed Shortest path Difference corresponds to the maximum allowed difference in shortest-path length between atoms of the two compared product graph vertices. Lesser values correspond to a more rigorous screening. By default this value is a unit bond.
   
   In 3D screening, the option Maximum Allowed Spatial Distance Difference corresponds to the maximum allowed difference in distances between atoms of the two compared product graph vertices. Lesser values correspond to a more rigorous screening. By default this value is 1 Å. The Number of Conformations option corresponds to the maximum number of outputted files of one molecule in different conformations and is to be used only for 3D screening.
   
   
3. Output
   
   According to the value of Number of highest ranked molecules to be written to the output (say W), LiSiCA will create mol2 files of that many (W) highest scoring target molecules with a comment section at the end of the file where the matching atom pairs are displayed. This value is by default 100. The resulting mol2 files are written into a time-stamp directory in the folder specified in Save results in:. By default this folder is the user's home directory. Also, a text file named lisica_results.txt with the target molecules with (in the descending order of) Tanimoto coefficients is written to the time-stamp folder.
4. Other settings
   
   The Consider Hydrogen options lets the user to choose if the hydrogen atoms are to be considered for the calculation of the similarity using the maximum clique algorithm. By default, hydrogen atoms are not considered in finding the largest substructure common to the reference and target molecules, so as to obtain the results faster.
   
   The Number of CPU cores to be used allows for the selection of CPU threads used by LiSiCA. By default, it tries to detect the number of CPUs available.

Load Project Tab

Output Tab

In the output tab, there are two listboxes. One contains ZINC IDs and Tanimoto Coefficients of target molecules in the decreasing order of the Tanimoto coefficient values. Any single target molecule can be selected on this listbox using a mouse click or using up/down arrow keys. The selected target molecule is displayed with the reference molecule on the PyMOL viewer window. Depending on the target molecule chosen on the first listbox, the corresponding atoms from reference and the target molecules are displayed on the other listbox. Any single pair of corresponding atoms can be selected on this listbox using a mouse click or using up/down arrow keys. The selected pair is highlighted on the PyMOL viewer window.

For 2D Screening, the two molecules (the reference and the selected target) are visualized side by side on the PyMOL viewer screen:



For 3D Screening, the 3D structures of the two molecules (the reference and the selected target) are superimposed using the PyMOL's pair matching function enabling easy visualisation of their similarities in the PyMOL viewer screen.

About Tab

Related Publications

A. Dilip, S. Lesnik, T. Stular, D. Janezic, J. Konc, Ligand-based virtual screening interface between PyMOL and LiSiCA, J. Cheminform., 2016, 8:46.

S. Lesnik, T. Stular, B. Brus, D. Knez, S. Gobec, D. Janezic, J. Konc, LiSiCA: A Software for Ligand-Based Virtual Screening and Its Application for the Discovery of Butyrylcholinesterase Inhibitors, J. Chem. Inf. Model., 2015, 55, 1521–1528.