SYBYL

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.

3. Delete backgrounds, if any:

   VIEW >>> DELETE ALL BACKGROUNDS

Read molecule 'atropine'

1. Read a raw model of atropine into work area M1:

   From the FILE >>> READ... menu,
   type ta_demo:atropine_raw.mol2 in the 'File to read' area. (Press OK)

   Alternatively, you may use your own sketch model of atropine. In that case, choose the name from the 'Files' box. Do make sure 'atropine' is read into workarea M1.

Setting up and submitting the minimization

1. Specify the energy parameters:

   COMPUTE >>> MINIMIZE...
   Press the MODIFY... button.
   Set the appropriate options to make the Energy dialog box looks like the one in Fig.8. In particular:
   - Select TRIPOS in the Force Field option menu,
   - Select GASTEIGER-HUCKEL in the Charges option menu.
   Press OK.

   

   Fig.8 Energy dialog box

2. The Minimize dialog box reappears. Set some of the minimization options using the Minimize Details dialog box:

   Press Minimize Details... button.
   Make the appropriate selections so that the dialog box matches the one show in fig.9. In particular:
   - Increase the maximum number of iterations to 1000.
   - Decrease the Non-bonded reset to 5.
   - Decrease the gradient threshold to 0.005.
   - Set the color option to Force.
   Press OK.

   

   Fig.9 Minimization details dialog box

3. The Minimize dialog box reappears. Submit the job for calculation:

   Type atropine_1 as the job name in Minimize dialog box.
   Select the SHORT 'machine' where the calculation is to be run.
   Check the RUN IN BATCH box. The dialog box should look like the one in fig.10.

   

   Fig.10 Minimize dialog box after changes

   Press OK.

   The minimization has now been submitted to run in batch mode. Proceed to the next step of this tutorial while this batch job is executing.

Optimizing a modified atropine model

1. Label non-H atoms:

   VIEW >>> LABEL >>> ATOM ID...
   Select ALL and change the logical operator UNION into DIFFERENCE
   Select ATOM TYPES... and toggle H on (Press OK to leave the Atom type selector box).

   Note that during the selection of atoms to be labeled, the atoms are highlighted.

   Press END on the Atom selector box

2. Modify torsion O9-C10-C11-C12:

   BUILD/EDIT >>> MODIFY >>> TORSION...
   Select atoms 9, 10, 11 and 12 subsequently, and note that the current torsion is written to the text area (180 degrees).
   Move the mouse into the Torsion angle value box and enter -60 (Press OK).

3. Optimize the modified model:

   COMPUTE >>> MINIMIZE...
   Type atropine_2 as the job name in the Minimize dialog box.
   Leave all other options unchanged.
   Press OK.

   The minimization of the modified model has now been submitted to run in batchmode also.

4. Finishing batch jobs:

   Finishing batch jobs signal to the user by messages such as:

   INFO: NetBatch job atropine_1 completed on machine cammsg1. INFO: Wed May 29 11:31:22 MDT 1996

   When both optimizations are done, i.e. the above message has appeared for both atropine_1 and atropine_2, you can continue comparing the results. Meanwhile, you could exercise rotating, scaling, and labeling the model or check the geometry using ANALYZE >>> MEASURE... and selecting one of the options presented.

Results

1. Comparing the results:

   Make sure all labels are turned off. (VIEW >>> UNLABEL... etc.)
   Use the RESET gadget to reset EVERYTHING.
   Use the Display Options gadget: , to set the screen in quartered mode.

   Read the results of both optimizations into workareas M2 and M3:

   FILE >>> READ...
   In the Read File menu, change the File Type ALL button into MOLECULE.
   Select atropine_1.mol2 and make sure m2: <empty> is highlighted. Press OK.
   FILE >>> READ...
   Select atropine_2.mol2 and make sure m3: <empty> is highlighted. Press OK.

   (Alternatively, if you have not been able to optimize both raw models of atropine, you can READ them from the ta_demo: directory as atropine_1.mol2 and atropine_2.mol2.)

   Three structures are now displayed. Try superimpose the models manually using the ringsystem of the raw model as reference point. Use the Work Area gadget to toggle the Display Area to be rotated from G to D1, D2, D3 and D4 and back to G.

2. Superimposing the optimized models with the results from the crystallographic analyses:

   BUILD/EDIT >>> ZAP (DELETE) MOLECULE.
   Select M1, the raw model (Press OK).

   FILE >>> READ...
   and type ta_demo:atropine_cry.mol2 in the 'File to read' area. (Press OK).

   Undisplay all H atoms using either the command line:
   undisplay m2(<h>)
   undisplay m3(<h>)

   or the equivalent from the menu (VIEW >>> UNDISPLAY >>> M2 >>> ATOM TYPE >>> H and pressing OK. Likewise for work area M3).

   ANALYZE >>> FIT ATOMS...
   Activate the ADD.. button and then select matching atom pairs from workareas M1 and M2 respectively.
   Choose only the ring atoms.
   Choose atoms from M1 first and then atoms from M2, making sure that the model in workarea M1 is used as reference.
   Select END from the atom selector box, when all pairs (8) are selected.
   Select SOLVE from the Fit Atoms menu and notice the model in work area M2 changing its orientation.

   Repeat this sequence for the models in work areas M1 and M3, using M1 again as reference.

   Change the display back to FULL from the Display Options menu, and try to color the molecules differently using VIEW >>> COLOR >>> ATOMS... and selecting all atoms from one work area and assign a specific color to the selected set.

   

   Fig.11 Final display

3. Comparing energies:

   Compare the potential energies of the two optimized models using:

   COMPUTE >>> ENERGY...
   and activating M2 (and later M3) and press COMPUTE.

   Note that the energy is written to the text window.

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

Other SYBYL tutorials: