Open another Terminal, give your PERM number and start SYBYL by typing sybyl. Resize windows so that this tutorial, SYBYL's graphical area, and the SYBYL's terminal screens are all visible.
In the 'File' menu, select 'Open'
Locate the MOL directory under the course directory, and select file AT.pdb.
Click OK to import the molecule.
This is the AT basepair. Now you will compute its energy. In the 'Compute' menu, select 'Interfaces -> MOPAC ...'
Select Method: PM3
Check 'None' for optimization, and add the keyword MMOK at the line 'Other Keywords'. See the picture below to verify that your options are correctly set.
Hit Submit to perform the computation. It will take about 5 seconds to finish the computation. The computer may beep when the calculation is finished and a message 'INFO: NetBatch job mopacfile completed...' appears on the Terminal screen below the SYBYL's main screen.
In the 'Compute' menu, select 'Interfaces -> Analyze MOPAC' Open the file mopacfile.syb and write down the Heat of Formation value. Hit Done to close the Analysis window.
Repeat this computation for A.pdb, T.pdb, GC.pdb, G.pdb, and C.pdb.
Delete the previous previous molecule by selecting Delete Molecule(s) from the Edit menu and read in the next structure. To compute the heat of formation, follow the procedure described above. You may see a warning like this:
Hit OK to overwrite the old output file.
Calculate reaction enthalpies for the formation of the AT base pair and the GC base pair based on computed heats of formation of six molecules. Are the result consistent with your expectations?
Even though reasonable results were obtained one should remember that the calculation you just did has significant limitations. First, in real DNA the free bases are hydrogen bonded to solvent water molecules and this interaction is expected to stabilize the unpaired state. Our calculation was performed in vacuo and thus neglected any DNA-water interactions. Second, the entropy of association can be a significant factor in determining the thermodynamic stability of molecular complexes, but our calculation considered only the interaction enthalpy. Third, real DNA is composed of negatively charged nucleotides but we modeled neutral nucleosides. The bottom line is that while calculations can provide useful insight, their results should be interpreted while keeping in mind limitations of the model and of the specific computational method.