Humboldt State University ® Department of Chemistry

Richard A. Paselk

Chemistry 432 - Spring 2002

BIOCHEMISTRY LABORATORY

Molecular Modeling III - Base-pair Hydrogen Bonding

For this exercise we are going to explore some weak bonding interactions, and how they can be predicted using modeling. Save all of your AM1 structures and surfaces so you can refer back to them!

This exercise is much easier to perform on the Macintosh with MacSpartan Pro than with PC Spartan Pro due to the Mac's cut and paste functions. There are only two Mac's with the program installed. They are located in the Molecular Modeling Lab, SA 562. Note that the programs on these computers are found in the folder "items for STUDENTS", while your own work will be stored in "STUDENT." (You may create your own folder in STUDENT.) Currently the computers in this lab don't save items to the server so if you want to save work you have two options: email it to yourself as an attachment (use Web Mail), or store it on a Zip disk. If you want to open files on the PC make sure you save them in Spartan exchange format and that your Zip disk is formatted for the PC (the Mac will read PC formated disks, but not vice-versa). The only part of this exercise that is really much more efficient on the Mac is the joining of the bases to make the H-bonded pairs. Thus if the Mac's are in use you may do all of the preliminaries of building and optimizing the models of the different bases on the PC. As with the Mac, save your structures as Spartan exchange, then send them to yourself with webmail.

The programs are quite similar, however the single-button mouse results in a number of operational differences, as noted below:

• Mouse click = PC left mouse-click
• Shift-click = "selection box" (use to copy and cut - not available on PC)
• Option-click = x-y translation with mouse movement (If no mouse movement, this will add a fragment at the pointer location - not available on PC)
• Apple-click = rotate in x-y plane with vertical mouse movement.
• Option-apple-click = zoom with mouse movement.

In order to simplify calculations we will build the various bases with a methyl group substituting for ribose. As an example, let's build 1-methylthymine.

• Select benzene by double-clicking on it under Rings on the kit palette, then click on the screen to add it.
• Go to Expert by clicking on its tab, then click and hold on the element to open the Periodic Chart, then select N. Now double-click on the bottom carbon of the benzene ring to convert it to a nitrogen (position 1). Next double-click on atom 3 to give the second ring nitrogen (note that in each case the nitrogen takes the valence and geometry of the carbon it replaces - this will be valuable later on).
• Now return to the Entry kit and select the sp³ C and add one to N(1) and a second to C(5).
• Now go to the Expert kit and select oxygen from the periodic chart, then select -x to give a single bond O and add oxygen to C(2) and C(4).

This completes the assembly of 1-methylthymine (note the bonding is not strictly correct, but this will be taken care of in the quantum calculations, though not necessarily displayed). You can now minimize it and run AM1 calculations and surfaces (density/potential) as you've done before (Molecular Modeling I - you may have to change the multiplicity). When you visualize the surface you'll find yet another PC-Mac difference: to change the surface "style" (Dots, Mesh etc.) you have to go to the Properties window under Display and click on the molecule to select it. The standard selection will appear in the lower left of the box.

Now construct a second methyl-base, e.g. 9-Methyladenine.

• Again start with benzene. Construct the second ring by first adding an sp² N (-N= the single bond will add to the ring, leaving the double bond exposed). Next add an sp² C (-C=) by clicking on the nitrogen double bond, then add a planar-trigonal N to the C single bond. Finally, seal the ring by selecting Make bond and clicking the two open bonds. You should now have a somewhat distorted, fused ring.
• Add a trigonal planar N to C(4) and a methyl carbon to N(9).
• Finally, convert C(1) and C(3) to nitrogens using the Expert kit as for thymine above, then use Delete to remove the hydrogens from these nitrogens.
• Minimize your structure and run AM1 and surface calculations on your structure to give a final model.

Construct models for 1-methylcytosine and 9-methylguanine and run AM1 and surface calculations as above.

We can now explore the possibilities for hydrogen bonding by opening any two of these models and matching opposite potential surfaces (aligning red-blue = negative-positive). The "ribose" residues should be far apart but on the same side of an axis passing through both bases. Once you have decided on how the bases line up you can construct the hydrogen bonded base-pairs.

As an example, open methylthymine and copy it, then close it. Now open methyladenine and use the Paste function to place the methylthymine on the same window. Now use the translate and rotate functions to align the two bases. Next select -H from the Entry kit and click on the open bonds of the hydrogen bonding nitrogens to add a hydrogen to each. Then use the Make bond function to bond the hydrogens to the appropriate oxygen or nitrogen to make hydrogen bonds. Finally, run an AM1 calculation.`Do not minimize these structures before running the AM1 calculations! You'll note that the bonding is not correct as constructed, so the mechanics program will try to make the "single" bonded oxygen bond angles 120°, for example. This is not a problem for AM1 since it will determine proper bond order (though it won't be displayed corrrectly) via calculating the proper wave-functions.

Questions: I will add some questions to this exercise later, which can be answered from the structures you have created, so save your work!

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© R. Paselk 2002

Last modified 31 January 2002