Week 4 HW: Protein Design Part I

Part A: Conceptual Questions

  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)
  2. Why do humans eat beef but do not become a cow, eat fish but do not become fish?
  3. Why are there only 20 natural amino acids?
  4. Can you make other non-natural amino acids? Design some new amino acids.
  5. Where did amino acids come from before enzymes that make them, and before life started?
  6. If you make an α-helix using D-amino acids, what handedness (right or left) would you expect?
  7. Can you discover additional helices in proteins?
  8. Why are most molecular helices right-handed?
  9. Why do β-sheets tend to aggregate? What is the driving force for β-sheet aggregation?
  10. Why do many amyloid diseases form β-sheets? Can you use amyloid β-sheets as materials?
  11. Design a β-sheet motif that forms a well-ordered structure.

Okay I am going to take a first pass through here just going off the lecture, wikipedia, and background knowledge I already have and then go back and try with AI assistance for the ones I have no answer for.

  1. A Dalton is another name for atomic mass unit. $6\times1023$ hydrogen atoms/dalton/atomic massunits is roughly $1g$ of mass, so $1g$ of amino acids is roughly $6\times1021$ amino caid molecues and 500g of meat should contain at most $3\times1024$ amino acid molecues. In reality, a good fraction of the mass of meat is water, fat, and other non-protein so the number will be less than that, probably between 10-30% of the max depending ont he meat involved, which gives a range of $3\times1023$ to $1\times10^24$ molecues.
  2. The state of being a cow is a complex relationship between a cow’s cells. Being a cow cell is a complex relationship between the DNA, lipids, and proteins in that cell as well as the cell’s history and its relationship to other cow cells. IN other words being a cow is a delicate state. Eating a cow (especially if we cook it first) involves destruction of the cells, relationships, and molecues breaking them down into component parts at a molecular level, in particular protein is broken down into its component amino acids so all the relationship,s structure, and patterns are lost and re-assembled into the patterns and structure of whatever is eating the cow by the machinery of the organisms and its cells (plus the injection of energy). You can acquire the molecular shadow of what you eat in the form of the isotope concentration of your components, e.g. if you eat at lot of corn (or things that eat corn) you will have the isotope ratio of a C4 plants like corn.
  3. Not sure there is a strict answer to this, because it seems like there is something of a historical contigency here. In fact my past seemed to indicate that different people cite differen numbers of “natural amino acids”, e.g. wikipedia says 22 amino acids instead of 20. Given that I think the best answer is something like early life must have existing in an environment where the current naturally occuring amino acids were being manufactured by some abiogenic process and ended up being incorporated into the structure of early proto-life. In addition to requiring that the amino acids was created by some abiogenic proces in decents amounts, the current amino acids of life are also the ones that life figured out how to internally synthesize. I can imagine there may have been a commonly occuring abiogenic amino acid that some proto-life started using, but proto-life didn’t figure out how to self-synthesize. As the abiogenic source of a hard to biologically synthesize amino acid waned, proto-life that used that amino acid would have been very strongly selected against, so even a common abiogenic amino acid may not show up as current “natural” amino acid.
  4. An amino acide is an organic compound that has both carboyxl and an amine group. This means that the to design an amino acid you can attach those groups to any organic/carbon backbone. For example, you could take octane (eight carbon atoms in a chain with hydrogen atoms) and attach a carboxyl and amine group to the last atom in the chain to make an amino acid (octine?). It is hard to tell if this is a “new” amino acid because there are 500+ amino acids just in nature according to wikipedia without a web/AI search.
  5. There are abiogenic processes that naturally create amino acids. One famous experiment put methane, nitrogen, etc in a jar and passed electricity through and ended up creating many organic compounds including amino acids. We have also detected amino acids and other organic compounds on remote comets/asteroids presumably created abiogenically by heating/cooling/light energy impacting on the frozen components like methane ice.
  6. I have no idea, but seems like D should be right-handed?
  7. I am not sure what this question is asking? Additional relative to what?
  8. Again, I am not sure what this question is asking? I assume they mean most biological molecular helices, because I don’t know that molecular helices have a preferred direction in general. If it is biological, I guess this is because some organic compounds are chiral and biology (because of historical accident?) selects/builds only one chirality of that organic compound. The chirality then impacts the shape formed when repeating units bind together leading to helices with a certain direction also.
  9. Not sure, but if I had to guess it would be hydrogen bonding between the parts of amino acids that are perpendicular to the direction of th sheet?
  10. No idea.
  11. No idea. Ok, no I will check/redo using outside research and AI especially for the last questions.

Part B: Protein Analysis and Visualization

Part C: Using ML-Based Protein Design Tools

C1: Protein Language Modeling

C2: Protein Folding

C3: Protein Generation

Part D: Group Brainstorm on Bacteriaphage Engineering

Part E: William and Mary Node Questions

  1. Be prepared to answer/discuss all 11 questions posed by Dr. Zhang. We will choose the most interesting ones to discuss in class.
  2. Be prepared to discuss the phage literature reading.
  3. A discussion of the phage literature will lead into our main discussion point: please be prepared to address and discuss the “big picture” question: how to apply these protein analysis tools to engineer a better bacteriophage. Please develop specific ideas for discussion.
  4. Time permitting - we will review final projects.