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Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot.
Version 1.0 of Ligand Depot supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool only works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.
This tutorial describes the different functions of Ligand Depot. It explains how to search for ligands present in the PDB, how to use the drawing tool, and how to search or browse a selection of other web resources that contain information on small molecules.
Using a single query, keyword searches based on chemical name or formula may be performed:
1) to search for small molecules that are part of the structures deposited with the PDB
2) to query a selection of other small molecule web resources that are search-enabled
The query options and results are described below.
Query options:
When searching for ligands based on their chemical name or formula, either exact or partial matches may be performed. For example, searching for the name "heme" and selecting the option of "equal" returns only those ligands that have a PDB compound name or synonym that matches the term "heme" exactly. However, if the condition "like" is used for the same query, then all ligands in the PDB that contain the word "heme" within their compound name or synonym are returned (e.g. heme, heme-as, heme d, diacetyldeuteroheme).
Similarly, entering the chemical formula "C34 H32 N4 O4 FE1" and selecting the condition "equal" will return only those ligands in the PDB that match that exact formula. However, if the condition "like" is selected for the same query, then all ligands in the PDB that contain the chemical formula are returned (e.g. "C34 H32 N4 O4 FE1" and "C34 H32 N4 O4 FE1 S1").
An additional feature that may be useful for finding ligands similar to a chemical formula of interest involves using a range of atom numbers within the formula. For example, entering the following atom number ranges "C34-36 H32-36 N4-5 O4-5 FE1" will return "C34 H32 N4 O5 FE1", "C36 H32 N4 O4 FE1", as well as other compounds whose atom numbers fall within the specified range.
Query results:
Ligand Depot returns two types of results from a single keyword search:
1) Query results are summarized as a list of PDB ligands with active links to more detailed ligand reports. In the query results, clicking on a 3-letter PDB ID (e.g. HEM) will return a ligand report for the small molecule of interest.
2) In a separate window, other web resources (e.g. ChemFinder) that may contain information on the small molecule of interest are also listed. Clicking on the active link for each resource allows the user to search each site individually. Alternatively, the user may choose the option of having all of the sites searched automatically. This is done by clicking on the 'Search' button. Please note that this search may take a few minutes.
How to search for ligands by chemical name or formula:
1. Select 'chemical name' or 'chemical formula' from the dropdown menu.
2. Select the option of matching the chemical name or formula exactly ("Equal") or partially ("Like").
3. Enter the chemical name1 or formula2 in the text box.
4. Click on the Search button.
5. Click on the 3-letter PDB ID of a ligand of interest in order to obtain more information about that ligand.
1Please note that searches are not case-sensitive.
2A range of atom numbers may be entered in the chemical formula (e.g. C34-36 H32-36 N4-5 O4-5 FE1), if desired.
Ligands may be searched using their assigned 3-letter PDB ID. For example, the small molecule heme has the PDB ID "HEM", whereas caffeine has the PDB ID "CFF". Please note that the assignment of PDB IDs is arbitrary and may not reflect the actual compound name or synonym in any way. For example, the PDB ID for tris-hydroxymethyl-methyl-ammonium is "144". It is also important to note that the 3-letter PDB ID may consist of 1 to 3 letters (e.g. "C" for cytidine-5'-monophosphate, "PT" for platinum).
Ligand IDs may be found at the bottom of PDB Structure Summary pages for those structures containing small molecules. They are also listed in PDB and mmCIF files. Alternatively, the PDB chemical component dictionary (see references below) lists compounds and their corresponding ligand IDs.
In the query results, clicking on a 3-letter PDB ID (e.g. CFF) will return a ligand report for the small molecule of interest.
How to search for PDB ligands by 3-letter ID:
1. Select 'PDB component id' from the dropdown menu.
2. Enter a ligand ID consisting of 1 to 3 letters.
3. Click on the Search button.
4. Click on the 3-letter PDB ID of a ligand of interest in order to obtain more information about that ligand.
A ligand may also be identified by performing a structural comparison between the ligand of interest and all of the small molecules present in the PDB. A graphical file containing a ligand's chemical structure may be uploaded into the drawing tool or else a molecule may be drawn from scratch. Ligand Depot performs the structural search by comparing the atoms and bonds of both the queried and target molecules. Once the structural comparison is performed the best possible hits are returned. The results may include either the actual ligand being queried, or else larger ligands that contain the queried molecule as a substructure. Therefore, the structural comparison will return a list of PDB ligands that are structurally similar, either in part or in whole. Please note that the chemical substructure search can only be performed on ligands present in the PDB.
Graphical file formats that may be uploaded into the drawing tool include the mmCIF format and the MOL format. A mmCIF format file holds the structural information about a specific molecule. It specifies the chemical identity of the molecule and lists its atom types along with their connectivity and corresponding bond orders. For more information on the mmCIF format, please see the references below. A MOL format file contains both the structural and geometrical information about a molecule.
How to find a PDB ligand by structure or substructure:
1. Click on the link 'Find a PDB ligand by structure or substructure'.
2. Please note that the current drawing tool only works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.
3. If a Java applet dialogue box appears, click on the "Grant Always" option to launch the drawing tool.
4. Select the type of ligand file (CIF or MOL) to be uploaded from the dropdown menu.
5. Use the Browse button to find the CIF or MOL-formatted file on the local machine.
6. Click on Load to upload the ligand file.
7. After the ligand appears in the drawing tool, select Clean Up Sketch.
8. Alternatively, instead of uploading a ligand file in CIF or MOL format, a ligand may be drawn from scratch using the drawing tool.
9. Modify the uploaded or sketched chemical structure as desired (see drawing instructions below).
10A. Click on the Add Hydrogens button to search for the exact chemical structure.
OR
10B. Click on the Remove Hydrogens button to search for small molecules that contain the substructure of interest.
11. Select Clean Up Sketch again.
12. Select Search Substructures.
13. Click on the 3-letter PDB ID of a ligand of interest in order to obtain more information about that ligand.
A graphical file containing a ligand structure may be uploaded into the drawing tool or else the molecule may be drawn from scratch. Graphical file formats include the mmCIF format and the MOL format. A mmCIF format file holds the structural information about a specific molecule. It specifies the chemical identity of the molecule and lists its atom types along with their connectivity and corresponding bond orders. For more information on the mmCIF format, please see the references below. A MOL format file contains the structural and geometrical information about a specific molecule.
How to use the ligand drawing tool:
1. Please note that the current drawing tool only works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.
2. If a Java applet dialogue box appears, click on the "Grant Always" option to launch the drawing tool.
3. Select the type of ligand file (CIF or MOL) to be uploaded from the dropdown menu.
4. Use the Browse button to find the CIF or MOL-formatted file on the local machine.
5. Click on Load to upload the ligand file.
6. After the ligand appears in the drawing tool, select Clean Up Sketch.
7. Alternatively, instead of uploading a ligand file in CIF or MOL format, a ligand may be drawn from scratch using the drawing tool.
8. Modify the uploaded or sketched chemical structure as desired (see drawing instructions below).
9A. Click on the Add Hydrogens button to search for the exact chemical structure.
OR
9B. Click on the Remove Hydrogens button to search for small molecules that contain the substructure of interest.
10. Select Clean Up Sketch again.
11. Select Search Substructures.
12. Click on the 3-letter PDB ID of a ligand of interest in order to obtain more information about that ligand.
The following drawing instructions represent the most common operations performed using the drawing tool:
A. Single bonds
Single bonds connecting carbon atoms may be drawn when the Bond button
is down and its icon shows a single bond. (The bond icon is a single line
in the bottom lefthand corner of the blue menu.)
B. Adding bonds
To add a bond, select
single bond mode (see above), then position the mouse pointer exactly on
the bond of interest and click. A new bond should appear. To change a single
bond to double (triple), click on the bond in the drawing once (twice).
C. Changing bond types
To select another bond type, hold the left mouse button down on the Bond icon until a second menu pops up. If making aromatic bonds, select Aromatic from the pulldown menu. Click directly on all bonds of the aromatic ring. After the last bond of the ring has been selected, an aromatic ring should form automatically.
D. Changing atoms
To
change an atom, press an atom button (e.g. B, N, O, F, etc.) in the blue
menu and then click on the actual atom to be changed in the drawing. Alternatively,
position the new atom type in the drawing and connect it to the main chemical
structure using the single bond mode described above.
E. Charged atoms
To increase or decrease a charge, select + or - in the menu and click
on the actual atom in the drawing. A red underline means that there is a
valence error.
F. Undo/Redo operations
Any operations may be reverted using the Undo option towards the upper righthand corner of the blue menu.
G. Additional hints
The User's Guide for the drawing tool is accessible by clicking on the question mark (?) in the upper righthand corner of the blue menu. Additional information on how to use the drawing tool may also be obtained here .
Query results are summarized as a list of ligands with active links to more detailed ligand reports. Each ligand report includes a chemical description, a two-dimensional chemical diagram, and a link to the ligand’s macromolecular Crystallographic Information File (mmCIF) which is found in the PDB chemical component dictionary (please see the references below). A ligand’s mmCIF dictionary description specifies the chemical identity of the molecule and lists its atom types along with their connectivity and corresponding bond orders.
PDB entries that contain a small molecule of interest are also listed in the ligand report and the PDB IDs are actively linked to their respective Structure Summary reports on the PDB website. The list of PDB structures containing the ligand is conveniently sorted by resolution and the coordinates for each ligand may also be downloaded in PDB, mmCIF and MOL formats for viewing in various molecular visualization tools.
Ligand Depot not only provides direct access to ligands in the PDB, it can also be used to browse several other small molecule resources on the Web. Currently, Ligand Depot stores information from 70 small molecule sites. The different resources are organized into four categories including nomenclature sites, molecular visualization sites, commercial sites, and chemical databases. Selecting one of these categories returns a list of web resources with a brief description of what each one has to offer. For example, selecting "chemical databases" returns a list of sites that includes Relibase and ChemFinder, among others. Each annotated list of websites allows the user to make an informed decision about which site to explore further and thereby retrieve information on small molecules more efficiently.
How to browse other sites:
1. Select the desired site type from the dropdown box.
2. Click on the Browse button.
3. Results are displayed in a new browser window.
4. Select a web resource of interest from the list of results.
5. The selected web site will be displayed in a second browser window and may then be searched for relevant information.
All of the websites listed in each of the four categories have been carefully selected based on their relevance. However, if you wish to refer a site that is not currently listed, you may do so by clicking on the link Refer a Site in the upper right hand corner of the Ligand Depot home page. Please include the name of the site along with its URL and a brief description. Also please indicate whether or not the site is search-enabled.
