Week 4 — Protein Design Part I

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)

Using an online converter ( https://www.unitconverters.net/weight-and-mass/gram-to-dalton.htm ), I calculated that 100 Daltons (1 amino acid) corresponds to approximately 1.66 × 10⁻²² g. After dividing the mass of a 500 g piece of meat by this value, I found the total number of amino acid molecules:

This means there are ~ 3.01 × 10²⁴ amino acid molecules in 500 grams of meat.

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

Humans eat beef or fish, but we do not become cows or fish because each species has its own unique genome. Eating proteins from another species does not change our DNA; our body simply digests the proteins into amino acids and uses them to build its own proteins. We only take the building blocks, not the instructions for making another species.

3. Why are there only 20 natural amino acids?

There are only 20 natural amino acids because the genetic code in DNA and mRNA is built to encode only these 20. Although there are 64 codons, many codons code for the same amino acid (redundancy in the genetic code). Scientists are experimenting with creating non-natural amino acids to expand the range of possible proteins, but in nature, only 20 are used.

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

I’m not completely sure how it works, but I remember from George Church’s slides that scientists can create new non-natural nucleobases. I guess that by using these artificial bases in the genetic code, it might be possible to produce new non-natural amino acids, although I don’t know the exact method.

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

Based on the information I found in this article https://doi.org/10.1002/chem.202201419 , amino acids existed before life and before enzymes, formed through non-enzymatic chemistry. Enzymes appeared later as proteins that accelerated chemical reactions, including the synthesis of other proteins. Experimental evidence for prebiotic amino acid formation comes from the Miller–Urey experiment, from 1953, in which gases such as CH₄, NH₃, H₂O, and H₂ were exposed to electrical energy, producing amino acids. ( https://www.britannica.com/science/Miller-Urey-experiment )

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

D-amino acids (D = dextro, right) are enantiomers, meaning they are mirror versions of L-amino acids (the natural amino acids in proteins, L = levo, left). If you make an α-helix using D-amino acids, the helix will be left-handed. Even though L-amino acids are “left” in configuration, when they form a helix they twist to the right because this is the most stable arrangement for hydrogen bonds and steric interactions. D-amino acids are mirror images, so their α-helix twists in the opposite direction.

7. Can you discover additional helices in proteins?

I’m not sure, but I guess it might be possible to discover additional or unusual helices in proteins that we don’t know yet. Methods like X-ray crystallography or NMR might reveal new structures, but I don’t know the details.

8. Why most molecular helices are right-handed?

Most molecular helices are right-handed because the natural amino acids in proteins are L-amino acids (left-handed in configuration). When L-amino acids fold into a helix, the right-handed α-helix is the most stable arrangement due to optimal hydrogen bonding and minimal steric strain.

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

β-sheets tend to aggregate because their backbone groups (NH and CO) can form extensive hydrogen bonds with neighboring strands from other molecules. The main driving force for β-sheet aggregation is hydrogen bonding, together with hydrophobic interactions, which increase structural stability and lower the overall energy of the system.

AI generated

10. Why do many amyloid diseases form β-sheets? -Can you use amyloid β-sheets as materials? Many amyloid diseases form β-sheets because misfolded proteins adopt β-sheet–rich structures that can form extensive hydrogen bonds between different molecules. This leads to stable aggregates called amyloid fibrils, which accumulate in tissues and cause disease. Yes, amyloid β-sheets can be used as materials because they form highly stable and mechanically strong fibrils. Scientists are studying them as biomaterials for nanotechnology and medical applications.

11. Design a β-sheet motif that forms a well-ordered structure. I am not completely sure how to design a specific β-sheet motif, but I would use amino acids that favor β-sheet formation, like valine and isoleucine. These amino acids are hydrophobic and have side chains that fit well in the extended β-strand structure, which helps the sheet stay stable. I would also alternate hydrophobic and polar residues, because in β-strands the side chains point up and down, so this pattern allows the sheet to interact with water on one side and form a stable hydrophobic core on the other. Together with hydrogen bonds between the strands, this could make a well-ordered and stable β-sheet.

1. Briefly describe the protein you selected and why you selected it.