2. What molecular properties increase the solubility of polar molecules in water? Which type of non covalent interaction is mostly involved in the presence of chemical groups containing oxygen, nitrogen, but not carbon atoms? What is the importance of hydrogen bonds in protein secondary structures? Which amino acid residues should you avoid when designing a water soluble peptide? How many amino acids do you need in a peptide to span a distance of 30 Angstroms in alpha helical conformation?

3. What is the melting temperature of DNA? Would you expect a melting temperature behavior of tRNA? What makes the base pairing of nucleotides in DNA precise? 

4. Draw the water structure and its hydrogen bond network around a (a)Na⁺ ion and (b)oil droplet.
What major difference in solute-solvent interaction would explain your solutions to problems a and b respectively?

5. Chargaff's rule says that the G+C content of DNA differs from organism to organism. You have extracted the DNA from two bacterial strains ('F' and 'H') which you found in a soil sample from Cuyuamaca State Park. A denaturation experiment shows that strain 'F' has a higher G+C content than strain 'H'. Draw the melting curves for both DNA's on a single figure and indicate them with 'F' and 'H'. If the melting temperature (Tm) of strain 'H' is 76 degrees Celsius, what could you say about the corresponding Tm of strain 'F'?

6. Using the single letter code, design a 15 amino acid peptide for each of the following properties (write the sequence only). You can choose only among the following 10 amino acids types (more than once, of course):

Ala, Val, Phe, Ser, Thr, Met, Glu, Asn, Lys, Pro
(a) Sequence of a peptide that shows a bend in the alpha-helix
(b) Sequence of a peptide which contains a sulfur group
(c) Sequence of a peptide which is soluble in a phospholipid membrane

7. You study the helical structure of a short piece of double stranded nucleic acid forming one complete helical turn, and is diluted in water buffered at pH 7.4, with sequence:
    5' A G G T C T A A C T 3'
    3' T C C A G A T T G A 5'
Give the name of the double helix type, the number of base pairs per turn, and the length of the particular piece of nucleic acid in Angstroms.

8. You are designing a small protein from two peptides with the following sequences:
   peptide I:      M S K F S C I R E 
   peptide II:     M F S T W C D
(a) Identify the non-polar residues in both peptides and give the net charge at physiological pH.
(b) Which peptide can span a phospholipid membrane (25 Angstroms thick) in (1) alpha helical form or (2) beta strand form:
(c) Give the possible  sequences of the small protein product after covalently linking the two peptides together.

9. Transfer RNA contains a fair amount of unusual bases (~25%). During the synthesis of a tRNA molecule, however, only ATP, GTP, UTP and CTP are used, but are posttranscriptionally modified by enzymes. Imagine a cell that is defective in an enzyme that methylates guanine bases in tRNA's. What would the effect be on tRNA-mRNA interaction?

10. Define the chemical bonds between units in the three major biochemical macromolecules: proteins, nucleic acids, polysaccharides. Write down the generic reaction equation for each type (substrate Û product) and name enzymes involved in the catalysis for both the forth and back reactions.

11. What effect drives the formation of phospholipid bilayers? Define the interior of the membrane by its dielectric property. What does 'amphipathic' mean, and how does this property relate to the stability of membranes? What can happen to amphipathic peptides in aqueous solution?

12. Cellulose Fibers are composed of many polysaccharide strands of several thousand glucose molecules. Monomeric glucose is water soluble, yet cellulose fibers do not dissociate from the supramolecular bundle into single strands. Why?

13. Explain how the specificity pocket of serine proteases affects the substrate-enzyme affinity, but not the k_cat of the reaction. Begin your answer with the definition of the enzyme specificity and end with an argument in favor of renaming the specificity pocket the 'affinity' pocket.

14. A Hill plot is used to determine if a protein shows cooperativity between subunits or not. How do you determine the Hill constant from the plot and how would the curve for a non-cooperative enzyme complex look like? Draw a Hill-plot for an enzyme with negative cooperativity.

15. Myoglobin and Hemoglobin belong to the same protein family. What level of structural information is usually used to define the evolutionary relationship between proteins? What other protein families do you know? Why can the tertiary structure for such analyses be more important than simple sequence?

16. How do the T and R conformation of the hemoglobin quaternary structure support a symmetric model o allostery?

17. What biological role(s) distinguishes Ca⁺⁺ ions from other (divalent) metal ions?

18. Explain the name 'serine/aspartate/cystein protease' (consult the chapter on the HIV protease for aspartate proteases).

19. You constructed a hydropathy plot of a not yet purified membrane protein (you know the sequence). You identified 6 hydrophobic stretches of at least 20 amino acids. What additional (structural) criterion do you need to know if those sequence fragments could be putative transmembrane spanning segments?

20. Explain the allosterism of the nicotinic acetylcholine receptor.

21. Bacterial porin channels contain 16 anti-parallel beta strands that form a b barrel. What could you say about the distribution of amino acids along the sequence to make the channel stable in membranes an suitable for the flux of hydrophilic molecules?

22. What are the basic concentration conditions of enzyme and substrate to measure V_max of enzymatic catalysis?

23. Explain one possible way of lowering the activation energy for an enzymatic reaction.

24. How does the tertiary structure of the chymotrypsin family of serine proteases affect the k_cat of the proteolytic activity?

25. You analyzed the specificity pocket of a new type of protease and found Lysine as part of it. What could you say about the sequence specificity of the protease?

26. What is the reason to find amphipathic helices on the surface of proteins/at the center of ion channel complexes like the acetyl choline receptor?

27. Ion channels can be compared to enzymes, even though they do not catalyze a chemical reaction? Describe the enzymatic mechanism of a ligand gated ion channel. What is the role of allostery in ligand gated channels?

28. The alpha subunit of Na-channels contains more than 2,000 amino acids. How many nucleosomes (approx.) would be needed to pack the gene coding for this protein into the chromosomal structure?

30. Why are cystein residues in globular proteins advantageous for the study of protein folding pathways in vitro?

31. The melting curve of a protein shows a sigmoidal transition from the native fold to the unfolded conformation. What is the mechanism behind this type of curve? Give an other example of such a process for a macromolecule which is not a protein.

32. Why is the helix of gramicidin A called a beta helix? What is unusual about its amino acids?

33. What is the driving force of self-assembly systems / protein-folding in water?

34. Thermal motion is important in enzymatic activity? Explain.

35. What is the packing ratio (stoichiometry) of Histones in a nucleosome core particle?

36. What type of amino acid residues are involved in nucleosome-nucleosome interaction? Which post-translational modification affects this interaction? What structural feature in the nucleosome crystal structure explains why histone-DNA interaction is not DNA sequence specific?

37. Macromolecular structures in cells can be shown to have self-assembly properties in vitro. In vivo, however, the assembly of those structures is often assisted by 'helper proteins'. What are these proteins called and give an example (for nucleosome assembly, for example).

38. What is the importance of having regions of high variability, like the CDR, on antibodies? On T-cell receptors?

39. How can he X-ray structure of the immunoglobulin fold help us understand that these regions of high variability don't affect the stability of the variable domain (compare this problem to the non related structures found in the chymotrypsin superfamily of serine proteases)?

40. What biochemical 'trick' was needed to solve the X-ray structure of immunoglobulins?

41. Which of the following protein(s) is not a membrane protein: class I MHC, T-cell receptor, IgG, IgM, muscarinic Acetylcholine Receptor, Myoglobin?

42. What are the major core constituents of N-linked oligosaccharides?

43. You study a new plasma membrane protein and try to identify its topology. You already predicted 7 potential transmembrane spanning segments. Based on the sequence analysis, how could you predict the inside-to-outside orientation of the protein, i.e., if the N-terminal domain is extra- or intracellular? What is the superfamily of proteins we are dealing with called?

44. What is the mechanism of lectin binding to other proteins? Can it bind any protein?

45. The movement of eukaryotic and prokaryotic flagella are based on different mechanisms. What is the energy source of each process?

46. How does a cell recognize if a protein has to be secreted or put into the plasma membrane?

47. How can a protease inhibitor be a potential drug suppressing the proliferation of HIV but not affect the host physiology?

48. What is the structural principle of a leucine zipper; what general feature of an alpha helix does it follow?

49. Explain the functional differences and similarities of Zn⁺⁺ ions in carbonic anhydrase and Zn-finger proteins.

50. Describe one of the motifs in the binding site of DNA binding proteins (interaction to major groove only).