An experiment was conducted to analyze the favorability of folding for a short p

Question

An experiment was conducted to analyze the favorability of folding for a short polypeptide consisting entirely of alanine. This polypeptide folds favorably into a single, continuous a-helix. If an individual alanine residue in the polypeptide is changed to glycine, A Garn for the folding of the a-helix increases by +1.88 kcal/mol. a. In which of the two peptides is a-helix assembly more favorable, the alanine-only peptide or the glycine-containing peptide? Briefly explain your answer. b. Briefly describe why the substitution of alanine with glycine affects the favorability of a-helix assembly in this way. Your answer must explicitly state whether the difference in favorability is primarily due to a difference in AH or a difference in Delta S_rxn for the folding of the alpha-helix. c. Does the hydrophobic effect contribute significantly to the favorability of alpha-helix assembly for the alanine-only peptide? Assume that the experiment is conducted in a dilute environment such that alpha-helices do not associate with one another. Briefly explain your answer If the N-terminal residue in the alanine-only peptide is changed to lysine (whose side chain is positively charged), Delta G_rxn for the folding of the alpha-helix becomes less favorable by 0.50 kcal/mol. Using what you know about the properties of alpha-helices, briefly explain why positioning a lysine at the N-terminus of an alpha-helix would decrease the favorability of helix formation.

Explanation / Answer

1) The free energy, delta G of a reaction , for a process to happen spontaneously is negative. Only , if the free energy is negative, the process occurs. But for cell functions, which largely are dependent on proteins and nucleic acids, the delta G is positive, i.e. endergonic reactions are carried out. Thus, the glycine - alanine peptide which has a higher positive free energy , this will be less favourable. Alpha helices are of 10-15 peptides. Entropic cost associated with the folding of this peptide will not be sufficiently covered by the hydrogen bonding . Thus, alanine only is more stable. Alanine has the greatest tendency to form stable alpha helices.

2) Here, the change is due to the enthalpy or delta H in the reaction. Enthalpy reflects the number and kinds of bonds in a molecule. Since, Glycine has a more bulkier group, it is less favourable to form the helix.

3) Assuming that the experiment is carried out in a dilute environment where they do not disscociate , implies that the hydrophobic interactions predominate. when this water is surrounding a hydrophobic molecule, there is optimal arrangement of the hydrogen bonds, thus making a highly structured shell called the solvation layer of water around the molecule. Since, alanine is a non polar amino acids, these non polar groups cluster together, as the extent of solvation decreases, resulting in a favourable increase in entropy.  

4) The positioning of lysine is going to make the alpha helix formation less favourable, since lysine is an amino acid with a polar side chain. Polar groups generally form hydrogen bonding with water and thus are soluble in water. Since there is only a single lysine molecule without any other partner with which it could bond, it destabilises the already attained conformation of the alpha helix.

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