Download 03-131 Genes, Drugs, and Disease ... 1. (10 pts, 10 min) The diagram on the left...

03-131 Genes, Drugs, and Disease
Problem Set 3
Due Sunday September 13, 2015
1. (10 pts, 10 min) The diagram on the left shows a small 12 residue
protein in its unfolded state (top) and its low-energy folded state
(bottom). Each circle represents an amino acid and the black
circles are non-polar residues. The mainchain is the red line.
a) Why is this state low in energy [Hint – where are the non-polar
residues]?
b) Draw the lowest energy form for the following protein. Does its “structure” differ from the first
protein?
2. (6 pts, 15 min) Rituximab is a drug that is used to treat certain types of cancer (you should use
web resources to answer this question).
a) What is rituximab? A small organic molecule, or something else?
b) Briefly describe how Rituximab works as a drug (be sure to cite your sources).
3. (5 pts, 5 min) A rare genetic disease results in an individual who has no T-helper cells. Will
such a person be able to produce antibodies to fight disease? Justify your answer.
Please view Jmol-a to answer the following two questions:
4. (5 pts, 5 min) The enzyme that is shown is ribonuclease, an enzyme that is released by your
pancreas to digest RNA contained in your food. The product of the digestion is nucleotide
bases, which your body can utilize to make RNA and DNA.
a) How many α-helices does this enzyme have? (Click on the button marked ‘a’) (yes this is a
simple question).
5. (8 pts, 20 min)The “wild-type” sequence refers to the sequence of a protein that is found in most
organisms. A mutation is a change in the genetic code for a protein that results in a change in
the amino acid sequence. A point mutant involves the change of one amino acid. A genetic
disease may occur if the mutation leads to a non-functional protein.
This question involves the valine at position 108 in the polypeptide chain. You may find it
useful to click on button ‘5’ before answering the following questions. The two surfaces that
you can place on the structure (+/- 108 Surf & +/- Packing) may also be helpful.
i) A mutation changes the valine at position 108 in ribonuclease to Alanine. How do you think
this will affect the stability of the protein? Will the alanine containing protein be more or less
stable than the wild-type? Briefly justify your answer with reference to the forces/interactions
that stabilize folded proteins. You can use the button labeled Ala108 to see what Alanine at
position 108 would look like.
ii) A person has a mutation in the DNA that codes for their ribonuclease enzyme. This mutation
converts Valine 108 to alanine. Based on your answer to part i), what disease condition
might exist in this person?
Please view Jmol-b to answer the following question:
6. (10 points, 20 min) This Jmol page contains the structure of a
complex between an immunoglobulin (antibody) and cocaine.
The chemical structure of cocaine is shown on the right. Only
the very top part of the immunoglobulin (Fv region) is shown
on the Jmol page.
a) Describe the general location of the binding pocket (area) for cocaine. Is it found
predominately on the light chain, heavy chain, or both? (2 pts)
b)
i) Describe the energetics of the interaction between Tryptophan33H and the bound cocaine.
Your answer should discuss what stabilizes the bound cocaine, e.g. H-bonds,
electrostatics, van der Waals, or the hydrophobic effect. (4 pts)
ii) Describe the interaction(s) between Tyrosine32L and the bound cocaine. Your answer
should discuss what stabilizes the bound cocaine, e.g. H-bonds, electrostatics, van der
Waals, or the hydrophobic effect (4 pts).