SYBYL

Clearing work areas

1. Clear all the molecule and display areas if necessary.

   BUILD/EDIT >>> ZAP (DELETE) MOLECULE
   If there is more than one molecule on the screen, click ALL, then OK to wipe them all.

2. Reset your screen if necessary.

   Use the RESET gadget to reset EVERYTHING
   Use the DISPLAY OPTIONS to reset to FULL screen mode.

1. Active the sketch menus and selct the first workarea in which to build the molecule.

   BUILD/EDIT >>> SKETCH MOLECULE...
   Select M1:<EMPTY> (press OK)

   When entering this mode, two menus appear: the 'Sketch Molecule Menu' and an 'Atomic Symbol Menu'. Your are placed in DRAW mode, automatically.

2. Display a grid to ease sketching. The grid has spacings of 1.54 Â, and scales with the molecule.

   Select GRID from the Sketch Molecule Menu

   This button can be toggled off by re-selecting it again.

1. Build the ring intuitively:

   Pick a point in space in the middle of the screen

   A highlighted cross appears, representing an unconnected atom. The highlight indicates that this atom is the point of attachment when a subsequent point is chosen as next atom. This is called 'coninuous drawing mode'.

   Pick another point above and right the first one
   Continue picking points to form a 6-membered ring as in fig. 2
   Close the ring by selecting the first atom again:

   

   Fig.2 6-membered ring

   When you close the ring by picking the first atom again, not atom is highlighted, indicating the continuous 'draw' mode is temporarily deactivated. Continuous draw mode is always suspended when an existing atom is chosen, whether it is the current atom of attachment or another atom. In the former case, no bond is drawn; while in the latter case, a bond is drawn and then continuous draw mode is deactivated.

2. Change the type of atom 1 to a nitrogen:

   Select N from the atomic symbol menu.
   Pick atom 1 on the sketched molecule.

   A label appears indicating that the type has been changed successfully and the atom is colored blue.

3. Introduce a third dimension to the molecule:

   Use the right mouse button an rotate the molecule about the x-axis until it has an orientation similar to that in fig. 3.

   

   Fig.3 Sketched molecule after rotation

   Select MOVE from the Sketch Molecule Menu.
   Select N in the ring and then pick a location that is somewhere above the ring.
   Select atom 4 and move it below the ring by the same amount.

   The molecule should now look similar to the one shown in fig.4., but don't be concerned if your structure is not a perfect 'chair'. The ring will be optimized later.

   

   Fig.4 Sketched molecule after moving atoms

1. Add bridge across the ring as shown in fig.5:

   Select DRAW on the Sketch Menu to return to continuous draw mode.
   Pick atom 2 as the current attachment atom.
   Pick a point below this atom and then another point diagonal to it.
   Pick atom 6 to close the ring.

   

   Fig.5 Sketched molecule with a bridge added

2. Clean up the ring system:

   Select TAILOR on the Sketch Molecule Menu
   Select CLEAN_UP (and press OK)
   Select 5_QUICK_MINIMIZE (and press OK)
   Press END
   Select CLEAN_UP on the Sketch Molecule Menu.

   There is an initial setup period while the minimizer parameters are being read from a database. Energy values are then printed in the text window after each iteration. The molecule display on the screen is not updated until the end of the minimization in order to reduce execution time. The minimization is complete when the "Existing atom or new point:" prompt returns in the text window.

1. Center the molecule on the screen:

   Select CENTER on the Sketch Molecule Menu.

   Rotate the molecule until its orientation is similar to the one in Fig.6.

   

   Fig.6 Sketched molecule with added chain

2. Add carbon chain to the ring:

   Select atom 4 as the current atom of attachment.
   Referring to fig.6, sketch the side chain by picking successive points at approximate locations on the screen for atoms 9 through 13.
   Pick atom 13 again to deactivate continuous drawing mode.

3. Draw double bond for the carbonyl group:

   Select atom 10 as the new point of attachment and then pick a point above and right of atom 10.
   Pick atom 10 again.
   The double bond appears and continuous drawing mode is deactivated since an axisting atom was chosen.

4. Add carbon to the nitrogen:

   Pick atom 1 (the nitrogen) the a point to its left.

5. Sketch the ester and hydroxyl groups:

   Select O from the atomic symbol menu and then pick each of the three atoms corresponding to those labeled O in fig. 7.

   The atoms are labeled O and colored red to reflect the change.

6. Add the phenyl group:

   Select GROUP on the Sketch Molecule Menu
   Select PHENYL and pick atom 11
   Select CENTER again

   

   Fig.7 Sketched molecule with phenyl group added and oxygens defined

1. Make sure atom 11 has a chirality of S:

   Select CHIRAL on the Sketch Molecule Menu and then select atom 11 (See fig.7).
   Select S (and press OK)

   If atom 11 is already an S chiral center, a message is displayed informing you of this and nothing else happens. If, however, the R chiral center has been sketched, the center is inverted to assume the proper stereochemistry.

2. Cleaning up using scan:

   Since the ring system has already been optimized, use the 4_SCAN option, which involves non ring bonds only, to clean up the model. (Note that any clean up option from 1 to 6 includes all options preceeding it in the list, therefore, all non ring bonds have their bond lengths and angles adjusted, and all torsion angles are scanned and adjusted to relieve bad contacts.)

   Select TAILOR on the Sketch Molecule Menu.
   Select CLEAN_UP (and press OK)
   Select 4_SCAN (press OK)
   Press END

3. Add hydrogen atoms:

   Select ADDH on the Sketch Molecule Menu.

   All atom and bond types are automatically converted to SYBYL types based on connectivity prior to adding hydrogen atoms.

4. Exit from the sketching mode:

   Select EXIT on the Sketch Molecule menu.

   A final clean up is done automatically every time you exit the Sketch Molecule menu.

5. Name the molecule:

   Select BUILD/EDIT >>> Name Molecule... and type ATROPINE (press OK)

6. Save the structure:

   Select FILE >>> SAVE AS... and type atropine (press OK)

   A file 'atropine.mol2' will be created. Note that the filetype is autmoatically added, and that the filename is case sensitive.

This concludes the small molecule sketching tutorial. We suggest that you repeat this tutorial on your own molecules of interest.

Other SYBYL tutorials: