| QSAR |
QSAR+ uses a study table to maintain and display the data for a QSAR analysis. Much like a conventional spreadsheet, a study table is made up of cells that can contain both numeric and textual data. Additionally, these cells can contain and display molecular structures. Each row in a study table represents a single observation (or experiment) and includes a molecular structure, user-entered biological activity data, and the results of descriptor calculations. For detailed information about the study table, see Chapter 5, Working with the Study Table.
Adding molecules to the study table
You can add molecules from the Cerius2 Models window to the study table by using the items in the Molecules menu in the study table:
To set charge calculation preferences
1. Click Charges... in the Molecule Preferences control panel.
2. Use the action buttons in the Charges control panel or select the appropriate Preferences button to edit and calculate charges with the current charging method.
2. Click Controls... next to the popup to open the OFF or the
MMFF preferences control panel:
For detailed information about using the Energy Minimization control panel and about the Cerius2·Minimizer module, refer to Cerius2 Simulations Tools.
To set conformation generation preferences
1. Click Conformations... in the Molecule Preferences control
panel.
2. Use the QSAR Conformation Generation control panel to select a default conformational search method, apply an energy cutoff, specify the number of conformations that will be generated, and so on. You can also use the Generate Conformers button at the top of the control panel to immediately generate conformations for all molecules, for only the selected molecules, or for only the current molecule.
For information about the Cerius2 Conformer Search and Conformer Analysis modules, refer to the Cerius2 Conformational Search and Analysis book. .
This section shows how to import molecules and their associated data from an SD file to the QSAR+ study table. The SD file format provides a general and flexible way to store chemical structures and data (biological activities, molecule name, values of calculated molecular descriptors, etc.), and QSAR+ offers functionality to take full advantage of these capabilities.
Loading molecules directly from SD files
To import molecules from an SD file select Molecules/From SD File... on the study table menubar (or from the Molecules menu on the QSAR card). The Add Molecules from SD File control panel appears:
The IMPORT MOLECULES pushbutton at the top of the control panel is initially inactive (grayed-out). The first thing you need to do to import molecules from an SD file to the study table is to select the SD file you want to import. You do this by using the file browser to navigate to the directory where the SD file is and then to select the file by highlighting its name with the cursor and clicking SELECT or by double-clicking the file. As soon as an SD file is selected, QSAR+ opens the file, counts the number of molecules in it, and displays this information at the top of the Add Molecules from SD File control panel. If the Read Data Fields checkbox is checked and if there is data in the file, the names of the data fields are also displayed in the panel.
The IMPORT MOLECULES pushbutton is only active after you have selected a specific SD file.
Selecting the range of molecules to import
You can import all the molecules in the file (the default behavior), a range of molecules, or only a single molecule from the SD file. You specify which option you want using the controls provided at the bottom of the panel.
If the Read Data Fields checkbox is checked when an SD file is selected, and if there is data in the file, the names of the data fields are displayed in the panel. You can then select any of the data fields to be added to the study table together with the corresponding molecules. These data fields appear as columns in the study table. To select data fields, you mark them with the cursor, using <Shift>- and <Control>-click to select groups of data fields. You can also use the Select All and Deselect All buttons to select and deselect all the available fields.
Another option that is provided is to assign one of the available data fields as the molecule name when reading the molecules from the SD file. To do this, make sure that only one data field is selected and click Set mol name from selected data field.
After the SD file has been selected and, optionally, data fields and a range of molecules have been specified, the molecules are loaded into the Cerius2 Models window and into the study table by clicking the IMPORT MOLECULES button.
All the molecule-processing options (hydrogen filling, energy minimization, charging, conformation generation) available for adding molecules from the Cerius2 Models window to the study table are also in effect when adding molecules from an SD file. You should check and activate only those options you want to use when importing the molecules from the SD file.
Special memory-saving options
Sometimes, specially when importing a large number of molecules from an SD file, it is convenient or even necessary not to keep all the molecules in memory. It may also be desirable not to keep in memory the study table row corresponding to each molecule. QSAR+ offers functionality to optionally delete each model from the Cerius2 Models window after it is added to the study table, and to optionally export the corresponding row to a file (after the desired molecular descriptors have been calculated) and delete the row from the study table.
You can access these options by clicking the Preferences... button at the top of the Add Molecules from SD File control panel. The SD File Preferences control panel appears: 
This control panel allows you to activate the options to delete both the model and the study table row after reading each molecule from the SD file. It also provides an option to control whether or not information regarding the SD file (file name, file type, and file index) is added to the study table.
Recovering deleted molecules
When you want to delete the models after adding them to the study table (see Special memory-saving options, above), there is a way to easily recover the molecules from the original SD file and include them in the Cerius2 Models window and in the corresponding row in the study table.
Select Molecules/Recover Molecules... in the Study Table. The Recover Molecules control panel appears: 
Select the rows for which you want to recover the corresponding molecules in the study table and click Reconstruct in the Recover Molecules control panel.
The information contained in the File name, File type, and File index columns in the study table is used to go back to the original SD file and extract the molecules, which are loaded into the Cerius2 Models window and into the corresponding study table cells.
This section shows how to add a set of structures from a Daylight SMILES file to the QSAR+ study table.
Loading molecules directly from Daylight SMILES files
This functionality is especially useful if the SMILES file contains a large number of molecules and loading them all into the model manager would require too much memory. Using a SMILES file and checking the Delete The Model After Adding checkbox (on the SMILES File Preferences control panel) can save memory that would otherwise be used to keep each molecule in memory.
To import a set of structures from a Daylight SMILES file, choose Molecules/From SMILES File... in the study table (or from the Molecules menu on the QSAR card). The Add Molecules from SMILES File control panel appears:
The IMPORT MOLECULES pushbutton at the top of the control panel is initially inactive (grayed-out). The first thing you need to do to import molecules from an SMILES file to the study table is to select the SMILES file you want to import. You do this by using the file browser to navigate to the directory where the SMILES file is, and then select the file by highlighting its name with the cursor and clicking SELECT or by double-clicking the filename. As soon as a SMILES file is selected, QSAR+ opens the file, counts the number of molecules in it, and displays this information at the top of the Add Molecules from SMILES File control panel.
The IMPORT MOLECULES pushbutton is only active after you have selected a specific SMILES file.
Selecting the range of molecules to import (Read mode)
You have the option to import all the molecules in the file (the default behavior), a range of molecules, or only a single molecule from the SMILES file. You specify which option you want with the controls provided at the center of the panel.
After the SMILES file has been selected and, optionally, a read mode selected, the molecules are loaded into the Cerius2 Models window and into the study table by clicking the IMPORT MOLECULES button.
All the molecule-processing options (hydrogen filling, energy minimization, charging, conformation generation) available for adding molecules from the Cerius2 Models window to the study table are also in effect when adding molecules from a SMILES file. You should be careful to check and activate only those options you want to use when importing the molecules from the SMILES file.
Special memory-saving options
Sometimes, especially when importing a large number of molecules from an SMILES file, it is convenient or even necessary not to keep all the molecules in memory. It may also be desirable not to keep in memory the study table row corresponding to each molecule. QSAR+ offers functionality to optionally delete each model from the Cerius2 Models window after it is added to the Study Table, and to optionally export the corresponding row to a file (after the desired molecular descriptors have been calculated) and delete the row from the Study Table.
You can access these options by clicking the Preferences... button at the top of the Add Molecules from SMILES File panel. The following panel appears:
This control panel allows you to activate the options to delete both the model and the Study Table row after reading each molecule from the SMILES file. It also provides an option to control whether or not information regarding the SMILES file (file name, file type, and file index) is added to the Study Table.
Recovering deleted molecules
In cases where you choose to delete the models after adding them to the Study Table (see Special memory-saving options), there is a way to easily recover the molecules from the original SMILES file and include them in the Cerius2 Models window and in the corresponding row in the Study Table.
To do so, you select Molecules/Recover Molecules... on the Study Table pulldown. The following panel appears:
Select (highlight) the rows for which you want to recover the corresponding molecules in the Study Table and click Reconstruct in the Recover Molecules panel.
The information contained in the File name, File type, and File index columns in the Study Table is used to go back to the original SMILES file and extract the molecules, which are loaded into the Cerius2 Models window and into the corresponding Study Table cells.
SMARTS table derivations
The following derivations can be entered as column headers in the study table:
==daysss(Structure, <SMARTS string>) and ==daysss_unique(Structure, <SMARTS string>)For example:
==daysss(Structure, "c1ccccc1") ==daysss_unique(Structure, "[C;H1]NOH")
Conformation refers to the placement in 3D space of the atoms and bonds in a molecule. Many of the descriptors that QSAR+ calculates are conformationally dependent (that is, they depend on the 3D structure of a molecule). Among these conformationally dependent descriptors, for example, are Molecular Volume (Vm), Dipole Moment (Dipole), and Principal Moment of Inertia (PMI).
If you have generated conformations for the structures in a Study Table, QSAR+ stores information about the generated conformations both in the Study Table and in a separate Conformers table for each structure.
Each row in a Study Table can contain information about only one conformation (that is, the current conformation) and its 3D coordinates. You can display and work with information about the other generated conformations by accessing the appropriate Conformers table. You can also update the Study Table with information about one of these other conformations (that is, you can select another conformation as the current conformation).
Displaying conformation information
This section describes the following activities related to displaying conformation information:
The Conformer Summary check box in the Conformers panel allows you to toggle ON and OFF the display of four conformation-related columns in a Study Table. For each structure in a Study Table, these columns provide the following information:
If you have generated conformations for the structures in a Study Table, QSAR+ can build a separate Conformers table for each structure. The Conformers table stores information about each of the conformations generated for a structure and contains one row for each conformation. Each table row contains the following information:
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The current row in the Conformers table identifies the conformation being used in the Study Table (that is, the current conformation).
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You can use the Conformers table to gather information about the highest and lowest energy conformations, to observe how a given 3D property is affected by various changes in conformation, to determine which conformations are within a specified kilocalorie range of the lowest energy conformation, and so on. You can also use the Conformers table to update the conformation that is currently being used in the Study Table (that is, to select another conformation as the current conformation).
You must have generated conformations for the structures in the Study Table to be able to display a Conformers table. Then you select the Study Table structure for which you want to display a Conformers table and do either of the following:
Just as with any Cerius2 table, you can use the icons on the table tool bar to work with a Conformers table. Additionally, you can click Update to rebuild the Conformers table (that is, to recalculate all of the conformationally dependent properties for each conformation of a structure). You might perform this activity, for example, if you previously interrupted QSAR+ processing before the Conformers table was completely built.
Recall that at any given time, the Study Table can contain only one conformation (that is, only one set of X, Y, and Z coordinates) for each structure. Conversely, a Conformers table contains information about all the conformations generated for a structure.
You can update the Study Table so that it contains information about another conformation by doing either of the following:
Displaying contingent descriptors
Contingent descriptors are those needed to calculate other descriptors. For example, density is equal to molecular weight divided by volume. Therefore, in order to calculate a value for the Density descriptor, QSAR+ requires the calculations for both the Molecular Weight (MW) and Molecular Volume (Vm) descriptors. In this example, Molecular Weight and Molecular Volume are referred to as the contingent descriptors.
QSAR+ stores information about contingent descriptors in the Study Table. You can toggle the display of these descriptors on and off, as appropriate.
To display contingent descriptors
Toggle the Contingent Descriptors checkbox in the Conformers panel ON and OFF to display or hide contingent descriptors.
