Answer any of the following questions by Shuguang Zhang:

• 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 is primarily composed of proteins, which are made of amino acids.

  • Assume 20% of meat is protein, meaning 500 g of meat contains 100 g of protein.
  • On average, one amino acid weighs ~100 Daltons (Da), or ~100 g/mol.
  • Since 1 mole = 6.022×10236.022 × 10^{23}6.022×1023 molecules, we calculate:

  100 g100 g/mol=1 mole of amino acids=6.022×1023 molecules\frac{100 \text{ g}}{100 \text{ g/mol}} = 1 \text{ mole of amino acids} = 6.022 \times 10^{23} \text{ molecules}

  100 g/mol100 g=1 mole of amino acids=6.022×1023 molecules

  Thus, a 500 g piece of meat contains approximately 6×10236 × 10^{23} of amino acids.

• Why there are only 20 natural amino acids?

  The 20 natural amino acids were evolutionarily selected due to:

  1. Optimal chemical diversity – They provide a good balance of hydrophobicity, polarity, charge, and flexibility.
  2. Efficient biosynthesis – They can be produced through robust metabolic pathways.
  3. Compatibility with ribosomes – The ribosome machinery evolved to recognize and assemble these 20 amino acids efficiently.
  4. Chemical stability – Some rare amino acids (like selenocysteine or pyrrolysine) exist but are not widely used due to instability or limited evolutionary advantage.

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

  Natural α-helices are formed by L-amino acids and are right-handed (dextrorotatory).

  If D-amino acids are used instead, the helix will be left-handed (levorotatory) due to the reversed chirality of the residues.

• Why most molecular helices are right-handed?

  This is due to the chirality of L-amino acids, which naturally form right-handed α-helices to minimize steric clashes and optimize hydrogen bonding.

  From an energetic perspective, right-handed helices are more stable for L-amino acids, making them evolutionarily favored.

• Why do beta-sheets tend to aggregate?

  β-sheets can stack due to specific interactions:

  • Extensive hydrogen bonding between adjacent chains.
  • Hydrophobic interactions that stabilize aggregates.
  • Planar structure that allows stacking.

  This tendency can lead to the formation of protein aggregates or amyloid fibrils.

  • What is the driving force for b-sheet aggregation?

    The primary driving force is the formation of a network of hydrogen bonds between polypeptide chains, combined with:

    • Hydrophobic interactions that stabilize aggregates.
    • π-π stacking of aromatic residues in β-sheets.

• Design a b-sheet motif that forms a well-ordered structure.

  To design a stable β-sheet, we can use a pattern of alternating polar and nonpolar residues, such as:

  Example sequence:

  Val - Ile - Ala - Gly - Ser - Thr - Val - Ile - Ala - Gly - Ser - Thr

  • Hydrophobic residues (Val, Ile, Ala) face one side, promoting aggregation.
  • Polar residues (Ser, Thr, Gly) face the opposite side, allowing solvent interaction.

  This structure ensures a well-ordered, stable β-sheet formation.

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

When we consume proteins, our digestive system breaks them down into individual amino acids. These amino acids are then used to build human proteins, following our own genetic instructions (DNA).

We do not become cows or fish because our DNA determines how the amino acids are reassembled, using the same building blocks but arranging them in a completely different way.

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

1. Fluoroamino acids – Fluorine-containing amino acids improve stability and alter reactivity.
2. Metal-functionalized amino acids – Such as ferrocysteine, which contains iron and could be useful in catalysis.
3. Expanded side-chain amino acids – Larger side chains that enable new types of protein interactions.

These synthetic amino acids have applications in protein engineering and biomaterials.

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

Amino acids could have originated from several prebiotic sources:

1. Abiotic synthesis – The Miller-Urey experiment showed that electrical discharges in a primitive atmosphere can generate amino acids.
2. Meteorites and comets – Amino acids have been found in meteorites like the Murchison meteorite.
3. Hydrothermal vents – These deep-sea environments are rich in energy and chemicals that could have catalyzed amino acid formation.

This suggests that amino acids were available before life emerged, forming the building blocks of the first biological molecules.

Can you discover additional helices in proteins?

Yes! While α-helices and β-sheets are the most common, other helical structures exist, such as:

• Π-helices – Wider than α-helices.
• 310-helices – More compact than α-helices.
• Coiled-coils and superhelices – Found in keratin and other structural proteins.

With AI tools like AlphaFold, it is possible to predict and discover new helical motifs in uncharacterized proteins.

• Why many amyloid diseases form b-sheet?

  Amyloid diseases (like Alzheimer’s and Parkinson’s) involve misfolded proteins forming β-sheet-rich aggregates.

  This occurs because β-sheets can stack into highly ordered, stable structures, which:

  • Resist degradation by cellular machinery.

  • Form fibrils that disrupt normal cell function

  • Can you use amyloid b-sheets as materials?

    Yes! Amyloid fibers can be used in biomaterials because they are:

    • Mechanically strong and highly stable.
    • Resistant to degradation, making them useful for long-term applications.
    • Self-assembling, which allows for nano-engineering applications like bioelectronics and drug delivery.