Week 4 HW: Protein Design Part I

1. Why are there only 20 natural amino acids?

There aren’t only 20 amino acids. There are just 20 that biology standardized early on in evolution. Proteins are built using translation. Once that system had evolved changing it was difficult because every protein in every organism depended on it. That creates evolutionary lock-in often referred to as a “frozen standard.” The current amino acids were selected due to their component atoms, functional groups, biosynthetic cost, use in a protein core or on the surface, solubility and stability. There are reasons for the selection of every amino acid.

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

Abiotic chemistry on early Earth. Amino acids are chemically natural products when carbon, nitrogen, hydrogen, oxygen, and energy mix. Meteorites can also contain amino acids, therefore, some could have come to Earth from space. Geochemical environments like hydrothermal vents, mineral surfaces, metal ions, heat gradients, and pH differences can drive reactions that form amino acids from simpler molecules. Before enzymes chemistry did the job.

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

4. Can you discover additional helices in proteins?

Yes there are algorithms that can scan protein structures and assign different helices based on hydrogen-bond patterns and geometry. Proteins contain more than just the regular α-helix. There are also rarer helices such as 3₁₀ helices, π helices, polyproline helices, and collagen triple helices. With computational design or mutation experiments, you can often convert loops or disordered regions into helices.

5. Why are most molecular helices right-handed?

Most molecular helices are right-handed because the building blocks of life are chiral molecules, and biology chose one handedness early on. Once that choice locked in, the geometry of bonding and steric constraints naturally favor right-handed helices for those particular molecular configurations. A right-handed α-helix lets hydrogen bonds line up cleanly while avoiding atomic collisions. A left-handed α-helix is theoretically possible but energetically unfavorable with L-amino acids.

6. Why do β-sheets tend to aggregate?

A β-sheet is a protein secondary structure where the backbone is stretched out into strands that sit next to each other, stabilized by hydrogen bonds between the backbone carbonyl and amide groups. The hydrogen-bond donors and acceptors often remain partially unsatisfied at the sheet edges. When another β-strand comes nearby, it can complete those hydrogen bonds. So strands stack. Then stacks stack. Then you get fibrils.
What is the driving force for β-sheet aggregation?
- β-sheet aggregation is driven by the combination of unsatisfied backbone hydrogen bonds seeking partners, hydrophobic interactions between sheet faces, favorable side-chain packing, and nucleation-dependent polymerization that lowers free energy as aggregates grow.

7. 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)