BME50A – W2016 – HW1 Question 1 Consider the following chemical structure of the peptide hormone oxytocin. What is the primary amino acid sequence of this peptide? (Hint: the C-terminus is modified by a process called amidation, which is the addition of an amide group. There is also a disulfide bond.) N-terminus, Cys (C), Tyr (Y), Ile (I), Gln (Q), Asn (N), Cys (C), Pro (P), Leu (L), Gly (G), C-terminus C-terminus amidation Disulfide bond between the two CysteinesQuestion 2 Linus Pauling, who was a fantastic scientist and winner of two Nobel prizes, is infamous for proposing a wrong structure of DNA. He published a paper proposing that DNA was a triple helix, with bases on the outside and phosphates on the inside (see image from their paper below). Based on chemical principles, what is problematic with this structure? Based on biological principles of DNA’s function, what is problematic with this structure?Chemical principles: phosphate groups are charged and repel each other. In the structure, they are clustered together in the middle of the molecule, which is highly disfavored. Biological principles: the sequence of nucleobases contain genetic information. But this structure does not imply how they can be copied. Furthermore, this structure has the nucleobases on the outside, so they are not protected from chemical damage Question 3 a) Consider a human cell, which is 15m in diameter. Assume the average length of a human protein is 350 amino acids. Using simple lengths of chemical bonds as your starting point, provide an estimate of how many proteins could fit in a cell if you totally packed a human cell with proteins. There are multiple approaches to this question depending on the assumptions you make. One approach is described below: 1. Average length of an amino acid is .8 nm Assume an amino acid is a sphere with radius .4nm Then the volume of an amino acid is .27 nm3 2. Average length of a peptide bond is .133 nm Assume the peptide bond occupies a sphere with radius .0665 nm Then the volume of a peptide bond is .0012 nm3 3. If the average protein has 350 amino acids and 349 peptide bonds then the volume of the average protein is (350*.27 nm3) + (349*.0012 nm3) = 95 nm3 4. If a human cell is 15 um in diameter, it’s volume is 1.76 x 1012 nm3 Thus by these assumptions 1.86 x 1010 protein molecules would fully pack into a single human cell b) Scientists have empirically found that you get ~0.2g of protein per mL of cell volume. Using this figure, calculate how many proteins are in each human cell. Mass of an average amino acid = 110 Da = .1 kDa Mass of average protein = 350 * .1 kDa = 35 kDaMW of protein = 35,000 grams/mole .2 g of protein per mL of cell volume = 2 x 10-22 g of protein /nm3 From previous question volume of cell is 1.76 x 1012 nm3 (2 x 10-22 g of protein /nm3 ) * (1.76 x 1012 nm3 ) = 3.52 x 10-10 g of protein per cell Number of protein molecules per cell = (3.52 x 10-10 g of protein per cell)/(1 mol of protein / 35,000 grams) *Avogadros # = 6.05 x 109 protein molecules per cell c) From your calculations from a) and b), how far can an average protein travel before hitting another protein in the cell? How many proteins would fit in that distance? - Percent Volume of the cell occupied by protein is 6.05 x 109/ 1.86 x 1010 ~=33% (6.05 x 109 is from b and 1.86 x 1010 is from a) - So 1 out of every 3 “volumes” in a cell is occupied by a protein molecule which means a given protein molecule can traverse the length of two proteins before running into another. - The volume of a protein from a) is estimated at 95 nm3. Assuming that a protein packs as a sphere, the diameter of a protein is 5.66 nm. Therefore, a protein will travel about 11.33 nm in one direction before hitting the next protein.Question 4 a) Steve Benner and colleagues are interested in designing nucleobases with non-natural hydrogen bonding patterns. Based on your knowledge of hydrogen bonding, predict base pairing interactions between pairs of these non-standard nucleobases. W pairs with Y X pairs with Z b) Given the structures of the four naturally occurring DNA bases (below), would you expect any the bases above to “cross-hybridize” with DNA bases? If so, which would pair with which? If not, why not? CHM / BCH 520: Chemical Biology (Fall 2015) Exam 1. 150 pts. total 1) a. Steve Benner and colleagues are interested in designing nucleobases with non-natural hydrogen bonding patterns. (e.g. Yang, Z. Benner, S.A. et al. Nucleic Acids Research 34, 6095, 2006). Based on your knowledge of hydrogen bonding, predict base pairing interactions between pairs of these non-standard nucleobases. (10 pts.) b. Given the structures of the four naturally occurring DNA bases (below), would you expect any the bases above to “cross-hybridize” with DNA bases? If so, which would pair with which? If not, why not? (10 pts.) NNOH2NNNHNNONH2NHMeNH2ONNHNNOH2NNNNNNH2NHNNNONH2NNNH2ONHNOOW X Y Z A G C T CHM / BCH 520: Chemical Biology (Fall 2015) Exam 1. 150 pts. total 1) a. Steve Benner and colleagues are interested in designing nucleobases with non-natural hydrogen bonding patterns. (e.g. Yang, Z. Benner, S.A. et al. Nucleic Acids Research 34, 6095, 2006). Based on your knowledge of hydrogen bonding, predict base pairing interactions between pairs of these non-standard nucleobases. (10 pts.) b. Given the structures of the four naturally occurring DNA bases (below), would you expect any the bases above to “cross-hybridize” with DNA bases? If so, which would pair with which? If not, why not? (10 pts.) NNOH2NNNHNNONH2NHMeNH2ONNHNNOH2NNNNNNH2NHNNNONH2NNNH2ONHNOOW X Y Z A G C T CHM / BCH 520: Chemical Biology (Fall 2015) Exam 1. 150 pts. total 1) a. Steve Benner and colleagues are interested in designing nucleobases with non-natural hydrogen bonding patterns. (e.g. Yang, Z. Benner, S.A. et al. Nucleic Acids Research 34, 6095, 2006). Based on your knowledge of hydrogen bonding, predict base pairing interactions between pairs of these non-standard nucleobases. (10 pts.) b. Given the structures of the four naturally occurring DNA bases (below), would you expect any the bases above to “cross-hybridize” with DNA bases? If so, which would pair with which? If not, why not? (10 pts.)