Week 4 HW: Protein Design- Part 1

How many molecules of amino acids do you take with a piece of 500 grams of meat? (on average an amino acid is ~100 Daltons)
Meat isn’t 100% protein; it’s typically composed of ~20% protein, ~20% fat, and ~60% water. So 500g of meat will approximately contain 100g of protein. Since Daltons is the unit used to measure the weight of small molecules and 1 Dalton is approximately $1.66 \times 10^{-24}$ grams. Since we need to calculate the number of molecules of AAs in our meat, let’s first convert the mass of one AA into grams: $$100\text{ Da} \times (1.66 \times 10^{-24}\text{ g/Da}) = 1.66 \times 10^{-22}\text{ g}$$ Then we divide the total protein mass by the mass per AA: $$\frac{100\text{ g}}{1.66 \times 10^{-22}\text{ g/molecule}} \approx 6.02 \times 10^{23}\text{ molecules}$$ So the total number of AA molecules in 500 g of meat is approximately $6.02 \times 10^{23}$, which is coincidentally (and elegantly) about 1 Mole of amino acids.

Thus we learn the trick that chemists use when going from molecular weights to weighing scale weights: If a molecule weighs 1 Da then 1 mole of it will weigh 1 gram. In this case since AAs weigh 100 Daltons, 1 Mole of AAs will weigh 100 grams (which is also the amount of protein in 500 grams of meat). Mind is BLOWN!

Why do humans eat beef but do not become a cow, eat fish but do not become fish?

Humans dont become cows because we dont incorporate bovine proteins directly. Through digestion, we break down those proteins down into their constituent amino acids. Since the 20 natural amino acids are a universal biological language, our body simply uses them as raw materials to build new proteins based on human DNA sequences.

There is a theory proposed by Crick that this is a frozen accident; Once life settled on 20, the cost of changing the entire genetic code was too high.
The other theory says that its the Optimal set; these 20 provide enough variety (acidic, basic, polar, non-polar) to build amost any functional shape. Adding more might have had diminishing returns or caused too many “side reactions”
As mentioned in the last slide of Joe Jacobsons lecture 20 provides the optimal balance of codon redundancy and diversity.

Every amino acid has the same basic structure: an amino group, a carboxyl group and a side chain (R-group). To design as new one, you typically keep the backbone the same so the ribosomes can still physically link it, but you can change the R-group to do something nature can’t. So lets design a “Metal-Sensing Amino Acid” since I am interested in how metals can be bound to proteins. For this we can use Bipyridine as our modified R-group because it loves to grab onto metal ions. And we can use UAG (stop codon) to code for our new AA. I found this paper titled “Rewiring Protein Synthesis: From Natural to Synthetic Amino Acids” and in it they describe that we need to modify two specific biological parts to make our synthetic AA. Firstly we need to evolve the Aminoacyl-tRNA Synthetase that are essential enzymes that catalyse the attachment of a specific amino acid to its corresponding tRNA. We can take a natural one and mutate its active site to fit our Bipyridine so it ignores the other 20 natural AA. The resulting tRNA is delivered to the ribosome by an elongation factor which we will have to modify to deliver our bulky new AA.

Where did amino acids come from before enzymes that make them, and before life started?
If you make an α-helix using D-amino acids, what handedness (right or left) would you expect?
Can you discover additional helices in proteins?
Why are most molecular helices right-handed?
Why do β-sheets tend to aggregate? What is the driving force for β-sheet aggregation?
Why do many amyloid diseases form β-sheets? Can you use amyloid β-sheets as materials?
Design a β-sheet motif that forms a well-ordered structure.