CHEM 331 Problem Set #2- Lehninger 5e, Chapter 4

Due Wednesday, September 19, 2012

Model 2: The dimerization of two alanines to form a non-covalent alanine-alanine

interaction in aqueous solution can be described by the following two processes and is
depicted in the picture below. It provides a simple model for the protein folding process.

Process 1: Formation of alanine dimer from two free, solvated alanines.

Process 2: Reorganization of water molecules from an ordered structure around
alanine methyl groups to being part of the bulk solvent.
In the model, water molecules with no lines are assumed to be part of the bulk solvent
and interactions between alanine molecules are not explicitly shown.

1. Consider Model 2 and complete the chart below (try to reason it out; use qualitative
measures, <0, >0, ~0):

  Process 1 Process 2 Overall

(alanine dimer) (water Dimerization
reorganization)
ΔH  

ΔS  

ΔG  
 
2. Consider the equation ΔG=ΔH-TΔS to discuss the overall thermodynamics of the
process. What is the biggest contribution to a favorable ΔG for the overall
dimerization (a combination of Process 1 and Process 2)?

3. Consider the peptide sequence used in the in-class activity:

 Leu-Glu-Glu-Val-Phe-Ser-Gln-Leu-Cys-Thr-His-Val-Glu-Thr-Leu-Lys

Discuss the expected stability of this helix in terms of the five constraints on α-
helices that are discussed in Section 4.2 of Lehninger.

4. The E2F family of transcription factors is important in regulating the cell cycle and
has a role in cancer. These DNA binding proteins have conserved helix-turn-helix
motifs that interact with DNA (Note: The DNA is represented as a stick diagram,
whereas the protein is represented as helical ribbons.) Consider the protein a-helix
indicated by the arrow. This helix is approximately 16 amino acids in length and runs
alongside the DNA. Suggest a sequence for this 16 amino acid helix and provide a
justification for your answer. Picture from Meinhart, A. et al. J. Biol. Chem.
2003:278:48267-48274 (used by permission). View this exercise as an opportunity to
practice scientific argumentation. Therefore the justification will be the most
important aspect of your answer.

5. Botulinum toxin, aka Botox, is a protein that is considered the most potent toxin ever
discovered. A very small segment of the sequence

Ala-Val-Thr-Ala-His-Glu

a. Draw the structure of this peptide at pH 7.3.

b. Estimate the pI of the peptide.

c. Analyze the ability of this peptide to form an α-helix and comment on its
relative stability.

d. How would mutation of the Glu to a Lys affect the stability of the secondary
structure?
6. Consider the following structure:

a. Write the primary structure of this peptide below:

b. Indicate the peptide bonds by placing an * next to each.

c. Draw dotted lines to show the hydrogen bonding that would occur if this
peptide adopted an α-helix.

d. Draw a polypeptide parallel to the one above, choosing amino acids that
enable you to show all of the types of interactions/bonds that could occur in
tertiary structure. Label each interaction.

e. For each tertiary interaction type, list how you would treat the protein to
disrupt that interaction (i.e., denature the protein).