Week 4 HW: Protein Design Part 1

Conceptual Questions – Answers

1. How many molecules of amino acids are in 500 g of meat?

Typical meat contains about 20% protein by weight. So for a 500 g piece of meat:

$$ 500 \ g \times 0.20 = 100 \ g \text{ of protein} $$

The average mass of an amino acid is approximately 100 Daltons. Since:

$$ 1 \ Dalton = 1.66 \times 10^{-24} , g $$

then:

$$ 100 \ Da \approx 1.66 \times 10^{-22} \ g $$

The approximate number of amino acids is therefore:

$$ \frac{100}{1.66 \times 10^{-22}} \approx 6 \times 10^{23} $$

So a 500 g piece of meat contains roughly:

$$ \sim 10^{24} $$

amino acid molecules (after proteins are digested).

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

Food proteins are not directly incorporated into our bodies.

Instead, they are broken down during digestion: protein → peptides → amino acids

These amino acids are then reused by our cells to build human proteins, according to our own genetic instructions: DNA → RNA → protein

In other words, food provides molecular building blocks, not ready-made biological structures.

Eating a cow is like receiving bricks, not a building.

3. Why are there only 20 natural amino acids?

The genetic code uses 64 codons, but these encode only 20 amino acids plus stop signals.

These 20 amino acids provide enough chemical diversity to build functional proteins:

  • hydrophobic residues
  • hydrophilic residues
  • charged residues
  • aromatic residues
  • flexible or rigid structures

Evolution stabilized around this set because it provides a good balance between chemical diversity and translational efficiency.

Some rare exceptions exist (for example selenocysteine and pyrrolysine), but the canonical system uses about twenty.

4. Can we make non-natural amino acids?

Yes.

Chemists and synthetic biologists routinely create non-natural amino acids.

Examples include amino acids containing:

  • fluorinated groups
  • photo-reactive groups
  • click-chemistry handles
  • metal-binding groups

These molecules can be incorporated into proteins using engineered:

  • tRNA molecules
  • aminoacyl-tRNA synthetases

This expands the chemical capabilities of proteins beyond what natural biology provides.

5. Where did amino acids come from before life?

Several hypotheses exist.

One well-known mechanism is prebiotic chemistry, demonstrated by the Miller–Urey experiment, where simple molecules such as

  • methane
  • ammonia
  • hydrogen
  • water

can react under energy input (lightning, heat) to produce amino acids.

Amino acids have also been detected in meteorites, suggesting that some may have arrived from space.

Another possibility involves hydrothermal vents, where mineral catalysis and heat may drive organic synthesis.

6. If an α-helix is made with D-amino acids, what handedness would it have?

Natural proteins use L-amino acids, which form mainly: right-handed α-helices

If the chirality is reversed and D-amino acids are used, the geometry of the peptide backbone flips and the helix becomes: left-handed

This is a direct consequence of molecular chirality.

7. Why do β-sheets tend to aggregate?

β-sheets expose hydrogen-bonding edges along their backbone. These edges can interact with neighboring sheets: β-sheet + β-sheet → stacked structure

This stacking is stabilized by:

  • hydrogen bonding
  • hydrophobic interactions
  • van der Waals forces

Because β-sheets are relatively flat structures, they pack easily into extended aggregates.

8. What is the driving force for β-sheet aggregation?

The main driving forces are:

  • backbone hydrogen bonding
  • hydrophobic interactions
  • van der Waals interactions
  • exclusion of water from the interface

Together these interactions stabilize stacked β-sheet structures and can lead to fibrillar assemblies.

9. Can amyloid β-sheets be used as materials?

Yes.

Amyloid fibrils are highly ordered and mechanically robust structures formed by stacked β-sheets.

Because of these properties, researchers are exploring their use for:

  • nanofibers
  • biomaterials
  • tissue scaffolds
  • bioelectronic materials

These systems exploit the natural ability of peptides to self-assemble into ordered architectures.