Week 4 Homework: Protein Design Part I

HW – Part A: Amino Acids and Protein Folding

4.1. Quantitative Consumption

Question: 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).

1 gram is equal to Avogadro’s number of daltons (6.022E23 Da). To find the total molecules in 500g of meat:

Total Daltons in 500g: 500g * 6.022E23 Da/g = 3.011E26 Da
Number of Amino Acids: 3.011E26 Da / 100 Da per molecule = 3.011E24 molecules

On average, you consume 3.011E24 amino acids per 500 grams of meat.

4.2. Biological Identity and Digestion

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

When we eat proteins from another organism, our body breaks them down into their individual building blocks called amino acids. These amino acids are then used by our native machinery to manufacture human proteins. While the raw components come from the fish or cow, they are used to build specific human proteins dictated by our own genetic code.

4.3. The Standard Genetic Code

Question: Why are there only 20 natural amino acids?

While there is not one comprehensive answer to this question, it is likely a result of evolutionary efficiency and competency. The 20 naturally occurring amino acids proved to be versatile, stable, and competent enough to support the plethora of life that they compose. They have handled the environmental changes of billions of years, so there were no significant evolutionary pressures for additional amino acids to arise in the standard code.

4.4. Non-Natural Amino Acid Design

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

Yes, it is possible to make non-natural amino acids by chemically altering the side chain or the backbone. For example, if I wanted an amino acid that I could tag and trace, I could modify the side chain with a molecule containing a recognizable chemical signature that also is a minimal hindrance to normal function.

As an example, the difference between phenylalanine and tyrosine is tyrosine’s alcohol (hydroxyl group) on the aromatic ring. A synthetic amino acid could be the tyrosine base but substituting the alcohol for a ketone, or adding a halogen that I could radiolabel and track. Another option is changing the hydroxyl group into methanol or ethanol to create a chemically viable alternative.

4.5. Prebiotic Origins

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

Before life started, Earth was a high-energy environment, constantly bombarded with meteorites and materials containing initial organic conditions. The planet was full of ammonia, water, methane, and hydrogen in reactive states. These were subject to UV energy from the sun and lightning, creating the conditions possible for stable molecules to form given the energy needed to achieve thermodynamic and kinetic stability to form more complex building blocks.

4.6. Chirality and Handedness

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

I would expect it to be left-handed, which is atypical from the norm. D-amino acids are the chiral enantiomers (mirror images) of L-amino acids, which are the ones naturally occurring in nature that form typical right-handed alpha-helix twists. Therefore, the mirror image of a right-handed twist would be a left-handed twist.

4.7. Right-Handed Helices

Question: Why are most molecular helices right-handed?

Molecular helices are typically right-handed because they are the most stable configuration for L-amino acids. Right-handed helices produce favorable hydrogen bond interactions and minimize steric hindrances, resulting in a molecule with greater thermodynamic stability.

4.8. Beta-Sheet Aggregation

Question: Why do beta-sheets tend to aggregate and what is the driving force?

Beta-sheets tend to aggregate due to favorable intermolecular interactions between the planes of the sheets. The driving force for aggregation is hydrogen bonding—the strongest intermolecular force—along with increasing dispersion forces as hydrophobic molecules layer together to limit their exposure to the aqueous environment.

4.9. Amyloid Diseases and Materials

Question: Why do many amyloid diseases form beta-sheets? Can you use amyloid beta-sheets as materials?

Parkinson’s, Alzheimer’s, and other amyloid diseases arise from protein misfolding that produce highly stable amyloid fibrils that layer into beta-sheets. These structures are thermodynamically favorable due to extensive hydrogen bonding and hydrophobic interactions between amino acid residues. This forms a durable structure that stacks into long, rigid fibrils which reduce protein function and disrupt cellular processes.

However, because these beta-sheets are so stable, they could be engineered into sustainable biomaterials. Potential uses include tissue engineering scaffolds, molecular meshes for water filtration, or potentially filaments for biological circuits.

Gemini AI was consulted for formatting