Sep 4 2023
Chemical similarity searching can be used to screen a database of compounds for structural similarity to a query chemical structure. The chemical similarity search window is shown below.
To access this window use the Tools/Chemical Search menu or select the button shown below.
To set up a query first you must have either drawn or loaded a chemical structure into ICM. Instructions for this are described in the Reading Chemical Structures and Molecular Editor sections of this manual. If for example the query molecule you want to search is in a chemical spreadsheet you can right click on chemical in the spreadsheet and select Query Molecule.
At this point your query can be modified as described in the Molecular Editor sections of this manual. However, there are a number of ways to specifically modify your query and filter your search. The way to accomplish this is to right click on a bond or atom and a menu as displayed below will be displayed. The menus differ depending on whether you right click on a bond or atom.
If you wish to specify a filter at an atom.
If you wish to specify a filter at a bond.
To specify a particular atom type, aromatic, aliphatic or R-group at a particular atom site.
To specify a particular number of hydrogen atoms at a particular site:
To specify the number of rings a particular atom will be a member of:
To specify the ring size connected to an atom:
To specify the charge at a particular point:
To specify an isotope at a particular atom
To specify the hybridization state of the atom:
To specify the number of atoms you wish an atom to be connected to:
To specify an attachment point - ie the position at which substituents will be added
An attachment point means that the atom can be attached to zero or more bonds to heavy atoms.
How to filter your query
To filter your query:
To add conditions to your filter:
To remove a filter, right click on the filter and select 'Remove Filter'.
To exclude a fragment from your search
Click on the option Exclude fragment list:
To begin processing your query first you need to decide which database to search. The options are listed in the Data Source section of the ICM chemical search window.
If you select MolCart you first need to setup the link to the correct database.
If you are searching a Table, click on the Table tab and then select the drop down button where the names of your currently loaded tables are stored.
If you are searching a File click on the File tab and then locate your local table database file .molt or if it is already loaded into ICM you can locate it with the drop down button.
Now select a search type:
A substructure search is a search whereby only the defined molecule in the query will be searched against the database. Whereas, a FP similarity search which stands for fingerprint search enables any fingerprint within a structure to be searched for in the database. The similarity method calculates Tanimoto distance using chemical fingerprints (1. -most distant, 0. - closest). The similarity = 1. - distance.
The Max distance option is available for use with the FP search and the Matches number option is for use with the substructure search. The option you do not require based on your search method will be blanked out. A "Max distance" value of 0 means that the search will only identify matches exactly the same as the fingerprint - the default is 0.4. The "Matches number" option allows you to stipulate how many times within a structure in the database your query can be found.
Additional options include:
If you make a selection of your query ICM can use that selection to search. How to make selections in the Molecular Editor are described here. Enter the Maximum number(#) of hits you would like returned.
Before processing the query determine how you would like your results displayed in the Results section of the Chemical Search window.
Count hits only - this option will count the number of hits and display this number in a window once the searching has been completed.
Select in source - If you are searching a table you can select and highlight the query in the source table that you are searching.
Hide unmatched - Hide unmatched will hide the compounds that were not matched from view.
Append - this option will allow you to append to current table, file or Molcart database.
To search a database by text enter the text you wish to search in the Text Search data entry box at the bottom of the ICM Chemical Search window.
Read about the Giga Search method here. The method will return as many hits as it can find in 15 seconds - you will then see a message asking if you want to run a longer more exhaustive search.
To substructure search Enamine's REAL database of >1.2 Billion Chemicals or MCules's ULTIMATE datbase:
Pharmacophores can be drawn in 2D in the ICM Molecular Editor or in 3D in the Graphical Display. 2D pharmacophore sketches can be used to search chemical tables (spreadsheets) containing 2D or 3D coordinates. A 3D pharmacophore can be used to search chemical tables containing 3D coordinates only.
Use the distance bond button and the add pharmacophore group button to sketch the pharmacophore. The distance bond button represents the number of bonds between each pharmacophore point. You can edit the distance by right clicking on the bond and selecting edit. Other groups such as aromatic can be added using the standard molecular editor buttons.
The easiest way to begin drawing a 3D pharmacophore is to draw a chemical in the ICM Molecular Editor which contains the key pharmacophore groups you want and then convert to 3D and extract the pharmacophore groups.
To draw a 3D pharmacophore this:
To move a pharmacophore group:
To change a pharmacophore group:
To make a new pharmacophore group:
The easiest way to make a new pharmacophore group is to clone a pre-existing one. To do this:
To change the direction of a pharmacophore group:
To remove the direction of a pharmacophore group:
To perform a pharmacophore search using a 2D pharmacophore:
To perform a pharmacophore search using a 3D pharmacophore:
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