This chapter describes ChemNote, the QUANTA application for building 2D molecules. Read this chapter if and when you plan to generate or significantly modify structures to use in QUANTA.
With ChemNote, you can create 2D molecular sketches that can be converted to 3D structures for use in other QUANTA applications. Sketches are created by progressively selecting and positioning various rings, bonds, and atoms, or by selecting and modifying sketches supplied with the application.
In addition to using drawing and editing tools in ChemNote, you can assign and display chemical properties such as partial atomic charges, saturation, chirality, isotopes, and cis/trans and axial/equatorial marks. The application also provides control over the display of carbon and hydrogen symbols within the sketch.
Information about a sketch is saved in a .mol file. ChemNote creates a .pct file that saves the 2D graphical data for continued use within ChemNote. ChemNote also creates a residue topology file (RTF) that is used by CHARMm to generate a principle structure file (PSF). ChemNote automatically names the RTF by capitalizing the first four letters of the .mol filename and adding a .rtf extension.
The ChemNote .mol file automatically converts to a molecular structure file (MSF) when you exit ChemNote and return to the Molecular Modeling application. This conversion also occurs when an existing .mol file is imported into Molecular Modeling.
ChemNote runs in a separate window that is opened over the startup QUANTA windows. Activity in Molecular Modeling mode is frozen until you return to the Molecular Modeling window.
If you have been working systematically through the tutorial exercises, the file newpeptide.msf is displayed in the viewing area.
ChemNote is started from QUANTA's menu bar.
To start ChemNote, display the Applications menu. Select Builders, open the pull-right menu, and select 2D Sketcher.
The ChemNote window is displayed over the QUANTA windows, which are frozen until you exit ChemNote.
The ChemNote window can be moved, iconified, pushed, and popped in the same manner as all other standard workstation windows. The window has these four distinct areas:
Although some window areas are the same as those of other QUANTA applications, the menu bar and palette are specifically customized for ChemNote.
The menu bar contains five menus, whose functions are summarized in Table 1.
ChemNote menus are displayed as pull-down or sticky menus. Tables 2 through 6 list the selections on each menu and briefly describe their functions.
The palette contains selections that you use to create and edit a 2D sketch. Use these tools either to perform various operations or to create actual sketch components such as atoms, bonds, and rings. The palette highlights the current selection. Table 7 lists and briefly describes the selections and tools.
In addition to the palette tools, ChemNote provides techniques for manipulating sketches. These include dragging a sketch or portion of a sketch with the right mouse button to reset it in the viewing area, or marking a sketch or portion of a sketch with a rubber band rectangle technique
Help messages are displayed at the bottom of the application window in the message line. Information is provided in dialog boxes displayed in the viewing area. These generally provide options for defining selection criteria.
Various rings and bonds are available from the palette to create 2D sketches. Using the mouse, you can add objects to the viewing area by making a selection from the palette, moving the cursor to the viewing area, and anchoring each object. You can move, rotate, or merge anchored objects with other objects.
ChemNote highlights atoms and bonds as the cursor is moved over them. This gives a visual cue to help select objects once they have been placed in the viewing area.
When you use the mouse to select and place various parts of a molecule, click rapidly. Delay in clicking the mouse can yield a different event.
Rings are defined from the palette by selecting one of nine available icons. ChemNote automatically assigns carbon atoms to each ring as it is drawn, and automatically supplies hydrogen atoms to meet valence requirements. Carbon and aliphatic hydrogen element symbols are not displayed by default. However, both carbon and hydrogen symbols can be displayed. Use the following practice exercise to become familiar with using ring tools.
1. Place a six-membered ring in the viewing area.
Move the cursor over one of the six-membered ring tools. Two graphical representations for each of the five- and six-membered rings are provided as a drawing aid. They have the same 3D conformation.
Click the left mouse button and a ring icon is highlighted, indicating it is selected.
Move the cursor into the viewing area. An image of the selected ring follows the cursor into the viewing area, replicating mouse movement. One atom in the ring is attached to the cursor.
Press and hold the left mouse button. The atom under the cursor provides an anchor point for the ring.
Continue to press and hold the mouse button as you move the cursor around the viewing area. The image of the ring rotates around the anchored atom as the image follows the cursor.
Release the mouse button. The ring is placed in the viewing area. The ring icon remains highlighted to indicate it is still selected.
2. Merge a second ring with the first ring.
Again, move the cursor in the viewing area. An image of a ring continues to follow the cursor.
Move the ring image over the ring already placed in the viewing area. The atoms in the placed ring are highlighted with a small square as the atoms in the ring image pass over them.
Move the ring image so two atoms are highlighted. Click the left mouse button. A second ring is merged with the first, joined at the bond between the two previously highlighted atoms. The ring icon remains highlighted to indicate it is still selected.
3. Turn off the ring selection.
Move the cursor over to the palette and the point icon. Click the left mouse button and the six-membered ring icon is no longer highlighted, indicating that the ring is no longer selected.
You can also turn off palette tools by positioning the cursor away from the structure in the viewing area and clicking the left mouse button twice.
Bonds are selected from the palette by clicking on one of seven available bond icons. ChemNote automatically assigns carbon atoms to each bond as it is drawn, and supplies hydrogen atoms to meet valence requirements. As with rings, carbon and hydrogen symbols are not displayed by default. However, both can be displayed.
Single, double, and triple bonds are displayed by icons of solid single, double, and triple solid lines, respectively. Resonant bonds are represented by an icon containing a solid and a dotted line.
Since ChemNote requires all atoms to be associated with a structure, a coordination bond icon that contains a single dotted line can be used to connect atoms that would normally exist without bond representation, for example, between sodium and the rest of the structure in sodium dodecasulphate.
Wedge bonds are used to define the relative position of side groups attached to an aliphatic ring. This allows you to position ring substitutes either axially or equatorially and build rings with substituents that are cis or trans to each other.
As described by IUPAC Rules and by Cahn, Ingold, and Prelog, filled wedge bonds extend from the display plane toward the viewer. Open wedge bonds extend from the display plane away from the viewer. The wide end of the wedge is closest to the viewer.
Using wedge bonds does not define chirality in ChemNote. You must specify R or S within atom properties for this purpose.
Use the next exercise to become familiar with using bond tools.
The atoms and bonds in the rings are highlighted with a small square as the cursor passes over them.
Move the cursor over the top-right atom in the structure and the atom is highlighted. Press and hold the left mouse button.
Drag the mouse and release to place bond; double click the left button to exit.
An image of the bond rotates around the anchor position, following the movement of the cursor.
The single bond icon remains highlighted to indicate it is still selected.
Press and hold the left mouse button. Move the cursor to position the bond image at an angle to the first bond. Release the mouse button and the second bond is placed in the viewing area.
The single bond icon remains highlighted to indicate it is still selected.
Move the cursor away from all objects placed in the viewing area, and quickly click the left mouse button twice.
The single bond icon is no longer highlighted, indicating the tool is no longer selected. The bond icon also can be turned off by selecting the point tool in the palette.
It is possible to use atoms other than default carbon and hydrogen atoms. Using the mouse, you can select other elements from the Periodic Table and place them in structures. You can also choose to display undisplayed carbons and hydrogens.
Carbon atoms are automatically assumed to be bond endpoints and ring members. These atoms can be changed to any other element contained in the periodic table.
Complete the following exercise to practice making a carbon atom substitution.
1. Change a carbon atom to oxygen
Move the cursor over the symbol for oxygen located in the palette. Click the left mouse button and the O is highlighted to indicate it is selected.
The atoms in the rings and bonds are highlighted with a small square as the cursor passes over them.
Move the cursor so that the atom located at the end of the second single bond is highlighted. Click the left mouse button.
The symbol OH is displayed near the atom, indicating the atom is now an oxygen automatically supplied with a hydrogen.
Select the point icon. The O tool is no longer highlighted, indicating the tool is no longer selected.
2. Display an undisplayed carbon atom.
The atom remains highlighted to indicate it is marked.
The symbol CH2 is displayed near the marked atom indicating the atom is a carbon with two automatically supplied hydrogens. The atom remains marked.
Hydrogen atoms are automatically supplied to meet valence requirements as additional rings or bonds are drawn. The actual number of supplied hydrogens is determined by an atom's ionic charge.
Hydrogen atoms do not merge with nearby hydrogen atoms when a ring is placed. Dependent hydrogens are automatically deleted when their associated atoms or bonds are deleted. Bond placement does not allow attaching a bond to an automatically supplied hydrogen or replacing a bond attached to an automatically supplied hydrogen with a new bond.
Complete the following exercise to become familiar with placement and display of hydrogens:
1. Change the display of the hydrogen atoms.
The symbol CH2 is changed to C and the hydrogens are now displayed separately.
The hydrogen symbols are removed from the display. The carbon atom remains displayed as C.
The group symbol returns to CH2.
2. Remove the mark on the carbon atom
This removes marks from all atoms and bonds.
Marks also can be removed by selecting Unmark All from the Edit menu.
The carbon atom and attached hydrogens are no longer highlighted, indicating the group is no longer marked.
3. Delete the oxygen atom and bond
Mark the oxygen atom and select the Eraser tool. The oxygen atom and its bond connections are deleted.
The CH2 group is changed to CH3, indicating another hydrogen was automatically added to the carbon when the OH group and bond were removed.
During the 2D to 3D conversion process, single or double bonds designated cis/trans or axial/equatorial are automatically placed correctly. Marking a bond and selecting either the Cis/Trans or Axial/Equatorial tools in the palette begin to cycle the bond through the available selections. Table 8, indicates the tools that are selected for each cycle.
|
1
|
Cis
|
Equatorial
|
|
2
|
Trans
|
Axial
|
|
3
|
None
|
None
|
You can determine what cycle these tools are in by the letter that appears in the middle of the bond. A marked bond will be identified by a c (cis), t (trans), a (axial) or e (equatorial) in the middle of the bond. A highlighted bond marked is opaque so it covers the bond indicator when it is activated. To see the indicator (c, t, a, or e), remove the highlighting by unmarking the bond.
Use the following exercise to practice marking bonds for the conversion process.
1.
Defining the merged ring bond as cis or trans
The bond remains highlighted to indicate it is marked.
A c is displayed on the bond, indicating the bond is defined as cis. The bond remains highlighted, indicating it is still marked.
A t is displayed on the bond to indicate the bond is now defined as trans.
2. Unmark the merged ring bond.
The bond is no longer highlighted, indicating it is no longer marked.
ChemNote allows only one structure to be saved at a time. It checks each sketch for the following before converting it to a 3D structure and saving it in a .mol file.
If a problem is found, ChemNote provides a dialog box prompt that identifies the problem and provides options for fixing it. For example, when a structure is saved, ChemNote checks that the total ionic charge of the structure is the same as the sum of the partial charges of the atoms. The net charge assignment number reported at the top of the dialog box represents the sum of the partial charges. The net charge number reported in the data entry field represents the sum of the ionic charges.
If the sum of the partial charges and the sum of the ionic charges are not the same, the dialog box provides several methods for adjusting partial charges.
After addressing these issues, ChemNote stores the 2D sketch in a .mol structure file. The application also creates a CHARMm RTF using the first four characters of the .mol filename as the RTF filename. To avoid ambiguity in RTF and residue naming, be sure that the first four characters of each .mol filename you create are unique. ChemNote checks against a list of known residues to prevent accidental duplication of names.
Use the following practice exercise to become familiar with the Save procedure.
A File Librarian is displayed.
The File Librarian disappears from the screen and a dialog box appears.
2. Smooth the partial charges over the specified atoms.
ChemNote checks the net charge and finds it does not equal the sum of the individual partial charges of the atoms in this structure. A dialog box enables you to select a method for adjusting the partial charges.
The desired net charge is: 0.000
CT, CH1E, CH2E, CH3E, C5R, C6R, C5RE, C6RE, HA types
The partial charges are changed, and new charges are saved in the trans.mol file. The sketch remains in the ChemNote window to provide the opportunity to use it as a base for creating another .mol file.
3. Change the merged ring bond to cis.
Select Cis/Trans and the t displayed on the bond is removed, indicating that the bond is neither cis nor trans.
A c is displayed on the bond, indicating the bond is defined as cis.
4. Save the structure and smooth the partial charges.
The File Librarian is displayed.
Enter the name cis in the File Librarian and click the Save button. Repeat the procedure in Step 2 for adjusting partial charges by selecting the default value and option in the dialog box that is displayed. Click the OK button to complete the procedure.
The dialog box is closed. The partial charges are changed, and new charges are saved in the cis.mol file. The sketch remains in the ChemNote window.
When the 2D sketch is completed, the structure contained in the .mol file is brought into the Molecular Modeling application converted to a 3D .msf file for further modeling and analysis. The conversion is done automatically when you return to Molecular Modeling mode.
If an MSF is active in the viewing area of the molecule window, from previous work, a dialog box is displayed that presents options for displaying the structure converted from ChemNote.
Table 9 lists the options in this box and provides a brief description of each.
Use the following exercise to become familiar with the process of moving a structure from ChemNote to 3D Molecular Modeling mode.
1. Return cis.mol to Molecular Modeling.
The ChemNote window is removed from the screen, revealing the Molecular Modeling window. The last saved structure in ChemNote, contained in the .mol file, is then automatically converted to an MSF.
2. Display cis.msf in Molecular Modeling
If you already have a structure displayed in the viewing area, a dialog box opens.
The structure is displayed in the Molecular Modeling viewing area. The Molecular Management Table is updated, and this information on the file is displayed in the textport:
31 atoms and 32 bonds read in
Setting bonding mode to use read-in connectivity
31 atoms selected for molecular structure cis.msf
31 atoms will be displayed
The Import selection in the File menu of the QUANTA menu bar allows you to import stored ChemNote .mol files. Complete the following exercise to become familiar with the import process.
1. Import the trans molecule into Molecular Modeling.
A File Librarian dialog box lists the available external file formats and a scrolling list of available files of each format.
The top scrolling list and filename field change to reflect your selection. The scrolling list contains the .mol files that are available for selection.
When the creation of trans.msf is complete, a dialog box is displayed so that the structure just created can be used.
The structure trans.msf is added to the display of cis.msf in the Molecular Modeling viewing area. Information about the active molecules is displayed in the textport.
2. Move one MSF away from the other.
Pick one atom - Reselect palette item tot qui. Pick atom to define center of moving fragment.
An ID is displayed next to the picked atom and the message line reads:
Fragment On
Undo Changes, Save Changes, and Reject Changes are activated in the Modeling palette. The Dial Emulator changes automatically to Dial Set 2.
Using the Y Translate dial, move the cis structure upward until it no longer overlaps the trans structure.
3. Save the new transformation of cis.msf
From the Modeling palette, select Save Changes and a dialog box offers saving options. Select the option Select new generation of cis.msf and click OK.
The old structure file is renamed cis.msf,001.
The Undo Changes, Save Changes, and Reject Changes selections in the Modeling palette are dimmed, indicating there are no changes needing action. The Dial Emulator returns to its default setting.
The structures in the viewing area are repositioned. Both structures are now visible, and the conformational differences are easy to see.
A template is any single connected structure of atoms and bonds that can be used as a building block for creating a new chemical structure. Templates are stored in standard ChemNote .mol files, each file containing one or more templates.
Templates allow chemical structures to be copied from the Template window and pasted into an existing sketch. The cut-and-paste procedure uses a clipboard that provides temporary storage for a template. The clipboard subdirectory is automatically created under your home directory. When a template is placed in the clipboard, it can be incorporated into the viewing area with the Paste selection from the ChemNote Edit menu.
The Template function opens from the ChemNote File menu. When it is selected, the Template window opens over the ChemNote window. Since you work in both windows to build a structure using a template, position the windows so both are visible on your screen.
The template window has five distinct areas:
Although some window areas are the same as in other QUANTA applications, the menu bar, title line, and buttons are specifically customized for the Template Viewer.
The title bar appears at the top of the window and contains the name of the current template file and the minimize/maximize button.
The menu bar contains three menus. Menu names and a brief functional description are listed in Table 10. Template menus are displayed as pulldown or sticky menus.
The buttons allow the keyboard to be used instead of the mouse for selecting a template, by entering an atom or element name in the data entry field located to the right of the buttons.
The Search button looks through the template file for the atom name that was entered in the data entry field, highlights the atom, and copies the template containing that atom to the clipboard. If there is more than one template with an atom of that name, the first one encountered is copied. If a name is not found, a message is displayed. The Clear button erases any text from the data entry field.
The following exercise involves building Orange II, the sodium salt of 4-(2-hydroxy-1-napthylazo) benzenesulfonic acid. Use this example to become familiar with the template, the editing, bonding, and atom functions, and the tools in ChemNote. Because of the ionic bond that sodium forms with the organic sulfate, the exercise also demonstrates the use of multiple MSFs.
This procedure creates the components for Orange II and then imports the structure to Molecular Modeling, where the CHARMm energy can be calculated.
1. Start ChemNote and the Template Viewer
In the Molecular Modeling window, display the Applications menu. Select Builder and then 2D Sketcher from the pull-right menu.
The ChemNote window is displayed.
The Template Viewer window is displayed over the ChemNote window. By default, a selection of carbocyclic group templates are displayed.
2. Select naphthalene from the Template Viewer window
Move the mouse so that the cursor is located in the Template viewing area. Move the cursor over an atom in the naphthalene structure and the atom is highlighted with a small square.
Copying...
indicating that the naphthalene structure is being copied to the clipboard. When the process is complete, the message line reads:
Structure copied to clipboard.
Move the mouse so the cursor is located in the ChemNote window. Display the Edit menu and select Paste.
The naphthalene structure is displayed in the center of the ChemNote viewing area.
The pasted structure may not be visible if the Template Viewer window is displayed over the center of the ChemNote viewing area.
Move the structure by placing the cursor over any atom or bond and pressing and holding the left mouse button while moving the mouse. To release and place the structure, release then click the mouse button.
Using the Point icon, drag a box around the naphthalene molecule selecting all its atoms. Then from the Layout menu select Atom Name.
All of carbon atoms in the molecule will be shown in their numbered sequence. Numbering is according to the build sequence for the molecule.
3. Add nitrogen to the structure.
Select N from the atom tools portion of the palette. Click the new carbon, changing it to a nitrogen.
4. Select and paste benzenesulfonic acid into ChemNote
Move the mouse so that the cursor is located in the Template viewing area. Move the cursor over an atom in the benzenesulfonic acid structure.
The atom is highlighted with a small square.
Copying
indicating that the benzenesulfonic acid structure is being copied to the clipboard. When the copy is complete, the message line reads:
Move the mouse so the cursor is located in the ChemNote window. Display the Edit menu and select Paste.
The benzenesulfonic acid structure is displayed in red in the center of the ChemNote viewing area.
Position the two structures so that the final nitrogen of the parent naphthalene structure and the nonsulfonic carbon of the benzenesulfonic acid structure are aligned end to end. Click the left mouse button to connect the two structures. Make sure the structures are bonded correctly.
Using the Point icon, drag a box around the naphthalene molecule, selecting all its atoms. Then from the Layout menu, select Atom Name.
All the nonhydrogen atoms in the molecule are shown in their numbered sequence.
6. Close the Template Viewer window
Move the mouse so the cursor is located in the Template Viewer window. Display the File menu and select Quit.
The Template Viewer window is removed from the screen.
7. Add additional oxygens to the structure
Move the mouse so the cursor is located in the ChemNote window. Select the single bond icon and add a single bond to the C9 carbon on the parent naphthalene structure.
A hydrogen is automatically supplied, creating an OH group.
8. Assign partial and ionic charges
Double click the new oxygen atom that is part of the sulfonic acid group. A dialog box for assigning properties opens. This box also can be opened by selecting Atom Properties in the Properties menu.
9. Return to Molecular Modeling.
Display the File menu and select Return to Molecular Modeling. Since the Orange structure has not been saved to a file, a dialog box asks if the changes are to be saved. Select the Yes button.
In another dialog box that prompts you to select the method for adjusting partial charges, enter the value: The desired net charge is: -1.000.
Select the following option CT, CH1E, CH2E, CH3E, C5R, C6R, C5RE, C6Re, HA types and click the OK button.
The ChemNote window is removed from the screen, revealing the Molecular Modeling window and a dialog box.
If any structures were displayed in the Molecular Modeling viewing area, they are removed and replaced by the structure orange.msf.
10. Return to ChemNote and create the ion file sodium.msf
The ChemNote window is displayed.
With the mouse, move the cursor to the ChemNote window and click on the screen, placing the sodium atom.
Double-click the sodium atom, and the Assign Properties dialog box is displayed. Select the following options:
12. Return the sodium ion to Molecular Modeling
Display the File menu and select Return to Molecular Modeling. Since this fragment has not been saved to a file, a dialog box asks if the changes are to be saved.
Enter the name sodium in the File Librarian and then click the Save button. A dialog box prompts you for the method for adjusting partial charges.
Select the following option CT, CH1E, CH2E, CH3E, C5R, C6R, C5RE, C6Re, HA types and click the OK button.
The ChemNote window is removed from the screen, revealing the Molecular Modeling window and a dialog box.
The ion sodium.msf is added to the Molecular Modeling viewing area along with organge.msf, and information on the structure is added to the Molecule Management table. A hydrogen has been removed from the sulfide group as a result of the charge adjustments made to the Orange molecule.
A dialog box allows you to choose the files you want to close.
Select the Close All button between the two scrolling lists. Both MSFs are moved into the Close scrolling list. Click the OK button.
Both structures are removed from the viewing area and saved in their respective MSFs. You will use them again in later chapters.
ChemNote is QUANTA's 2D molecular sketching application. The application runs in a separate window that is opened over all QUANTA windows. Other activity in QUANTA is frozen until ChemNote is closed.
In ChemNote, sketches are created by progressively selecting and positioning various rings, bonds, and atoms or by selecting and modifying templates supplied with the application. Templates are accessed through a template window.
Chemical properties such as partial atomic charges, saturation, chirality, isotopes, and cis/trans and axial/equatorial geometry can be assigned in ChemNote. The application also provides control over the display of carbons and hydrogens within the sketch.
Any 2D sketch created in ChemNote is automatically converted to a 3D structure in a .mol file when the structure is moved into the Molecular Modeling application. ChemNote creates a .pct file that saves the 2D graphical data for continued use within ChemNote. The application also creates an RTF that is used by CHARMm to generate a PSF. The ChemNote .mol file automatically converts to an MSF when ChemNote is closed and Molecular Modeling reactivated. This conversion also occurs when an existing .mol file is imported into Molecular Modeling.
