Week 4 HW: Protein Design I

Part A : Conceptual Questions

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)

Amino Acids are protein building blocks, so whatever percent of protein the meat contains is technically the AA content. A quick google search tells me that most cooked meats contain 20%-30% protein by weight. I’ll take 25% as my number. Now, 25% of 500g is 125g. (500/4)

Amount of protein = 125g

Now, 1 AA avg. = 100 Daltons. but 1 Dalton = 1 g/mol

so 1 AA = 100g/mol. To find the amount of moles = mass / molar mass

therefore, No. of moles of amino acids = 125 / 100 = 1.25 moles

number of molecules = moles x Avogadro’s Number = 1.25 x 6.022 x 10^23

= 7.527 x 10^23 molecules of amino acids per 500 grams of meat.

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

The proteins from other animals are built out of the same universal building blocks and the process of digestion breaks food down into the building blocks. (catabolism) These building blocks are then used to make YOUR own proteins using YOUR DNA. (metabolism) Basically:

When humans eat cow, human body not take cow protein. Human body break down protein into free amino acids. Free amino acid used by human body to make its own protein. Free amino acid not make a human a cow or fish.

3. Why are there only 20 natural amino acids?

They’re basically evolution-wise frozen in place. Early life settled on 20 AA that were chemically diverse enough to build different functional proteins. Once the genetic code was ’locked’ There was no way that evolution could now swap it, it would break everything. 20 amino acids have enough chemical variety to accomplish the protein goal.

4. Can you make other non-natural amino acids? Design some new amino acids.

Yes, it is possible to make new amino acids, labs do this using engineered tRNAs that insert a non-natural AA at the stop codon. An example of a new amino acid created by modifying the side chain is ‘fluorophenylalanine’ - it is basically a phenylalanine with a fluorine atom, making it more stable and UV trackable.

5. Where did amino acids come from before enzymes that make them, and before life started?

The Miller-Urey experiment has shown that lightning + early earth atmosphere could form amino acids spontaneously. Also amino acids have been found in meteorites like the Murchison meteorite, which could indicate that amino acids could’ve come from space. Amino acids aren’t strictly a product of life, but rather a tool life used.

6. If you make an α-helix using D-amino acids, what handedness (right or left) would you expect?

Naturally, α-helixes made from L-amino acids have right handed turns. So logically if we were to use D- amino acids to make α-helixes then they should have left-handed turns.

7. Can you discover additional helices in proteins?

Skipped.

8. Why are most molecular helices right-handed?

Most molecular helices are right handed because the life uses L-AAs. the geometry of L-AAs favors right handed twisting when they form hydrogen bods along a backbone. It is just like the answer of Q.3, L-AAs dominated in the early life and that dominance carried over.

9.Why do β-sheets tend to aggregate? What is the driving force for β-sheet aggregation?

β-sheets have exposed hydrogen bond donors and acceptors along their edges. So when 2 β-sheets meet edge to edge, they form hydrogen bonds with each other and grow in to ordered stacks. The driving forces of this bonding are 1. Hydrogen bonding 2. Van der Waals interactions between sheets 3. Hydrophobic effect - water shoves the sheets together to get those nonpolar faces out of its way.

10. Why do many amyloid diseases form β-sheets? Can you use amyloid β-sheets as materials?

Once a protein misfolds, it can cause other copies of the same protein to misfold in the same way. In cases of misfolds, sometimes a β-strands edge can get exposed, this edge then acts like a template and causes the other proteins to misfold the same way and forms a stack, the stack keeps growing. The result is insoluble amyloid fibrils. Diseases like Alzheimer’s (Aβ plaques), Parkinson’s (α-synuclein), all involve this.

The same reason why amyloid diseases are pathological make them useful. Aggregate materials can be incredibly stable and heat resistant. They’re perfectly ordered. They are self-propagating/assembling.