Week #4 (Due Sunday, Feb. 8)

An amino acid can be present in two forms: the un-ionized form, H2NCHRCO2H, and the Zwitterion, +H3NCHRCO2-. A zwitterion is a molecule which contains charged groups but which as a whole is neutral.

You will explore the properties and the relative stability of the two forms in the case of the simplest amino acid glycine. A series of calculations will be performed on each structure. You will find the following sequence of operations to be useful after drawing the structure: save the file using Save As, define the calculation, and perform it using Submit. This approach will guarantee that you will end up with a Spartan file for each step of the calculations.

I) Calculations on glycine in the Zwitterion form, +H3NCH2CO2-.

A) Draw the structure of your amino acid using the Peptide feature of the Build menu. Use the Terminate feature to properly define the charges at the termini.

B) Minimize the energy of the structure using Molecular Mechanics with the Merck Molecular Force Field. The Calculate Field of the Setup menu should be set to Equilibrium Conformer. Comment on the conformer produced by the minimization. Why this particular conformer? Measure the bond lengths, bond angles, and torsional angles.

C) Re-minimize the structure obtained in step (B) using a semi-empirical quantum mechanical method (Calculate à Semi-Empirical) and an AM1 Hamiltonian. Measure the bond lengths, bond angles, and torsional angles of the resulting structure. Compare these values to the structure from part B and literature values.

The crystal structure for the three forms of glycine (+H3NCH2COO-, H2NCH2COO-, and H3NCH2COOH ) was extracted from the Cambridge Structural Database and is in the file ‘glycine.pdb’. You can use Spartan to open the file.

II) Calculations on glycine in the un-ionized form, H2NCH2CO2H.

A) Draw the structure of your amino acid using the Peptide feature of the Build menu. Use the Terminate feature to properly define the terminal groups.

B) The unionized species is conformationally more flexible. Perform a search of low energy conformers. The Calculate field of the Setup menu should be set to Conformer Distribution. After completing the calculation load (File à Open … should find file with .Conformer suffix) the spreadsheet created by the process and examine the low-energy conformers.

To display the molecules and energies:

1) Choose Display à Spreadsheet

2) Add à E à kcal/mol à OK

3) Energies of the conformers should appear in the spreadsheet

To graph the energies and molecules

1) Choose Display à Plot

2) In window choose Molecule for the X-axis and E for the Y-axis à OK

Consider the most direct conversion of the Zwitterion to the unionized form. The hydrogen on the –NH3+ that is closest to a carboxylate oxygen is transferred as a proton to that oxygen. Examine several low-energy conformers and find the conformer that matches the description of this species. Is it the conformer with the lowest energy? Examine the energies of other low-energy conformers and compare and contrast their structures.

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