Week 4 HW: Protein Design Part I
Part A. Conceptual Questions
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)
Answer: On average, raw meat is ~20%-25% protein by weight, say we take it to be 20%, in the 500g sample we have, we will have 500*0.20 = 100g of protein. 1g = 6.022e+23 Daltons, so 100g = 6.022e+25, and then: # of AA = 6.022e+25/100 = 6.022e+23 AAs!
Why do humans eat beef but do not become a cow, eat fish but do not become fish?
Answer: First of all the cells in the fish and beef are usually dead due to denaturation from heat, so no active process can come from there. There is also no gene transfer from dead cells to humans. Additionally, say that somehow the DNA transfers to our cells, it will be detected as a pathogen way before it gets there, and if it does, there is no mechanism to embed the DNA to our own DNA, and also it will not knock out our own DNA so the worst case will be a combination of homosapience and cow or fish. 4. Why are there only 20 natural amino acids? 5. Can you make other non-natural amino acids? Design some new amino acids. 6. Where did amino acids come from before enzymes that make them, and before life started? 7. If you make an α-helix using D-amino acids, what handedness (right or left) would you expect? 8. Can you discover additional helices in proteins? 9. Why are most molecular helices right-handed? 10. Why do β-sheets tend to aggregate? What is the driving force for β-sheet aggregation? 11. Why do many amyloid diseases form β-sheets? Can you use amyloid β-sheets as materials? 12. Design a β-sheet motif that forms a well-ordered structure.
Part B: Protein Analysis and Visualization
1. Briefly describe the protein you selected and why you selected it.
Answer: Nav1.7 is a voltage-gated sodium channel located in neuronal membranes that initiates and propagates action potentials by allowing Na⁺ ions to enter the cell in response to changes in membrane voltage. It plays a crucial role in controlling the excitability of nociceptor neurons and is therefore essential for the sensory perception of pain. This protein demonstrates a clear relationship between 3D structure and electrical function and has significant physiological and clinical relevance. I was particularly drawn to it because of my interest in understanding how the brain works and because its structural properties provide an opportunity to explore the mechanisms underlying neuronal signaling.
2. Identify the amino acid sequence of your protein:
Here is the AA sequence of Nav1.7:
As shown in the structure, the Nav1.7 complex includes auxiliary beta subunits that regulate channel function (chains B and C). For the purposes of this assignment, I will focus on chain A, which corresponds to the alpha subunit forming the pore and voltage-sensing domains of the channel!
- How long is it? 2031 AAs!
- What is the most frequent amino acid? L, Leucine, which appears 202 times.
- How many protein sequence homologs are there for your protein? Since the UniProt BLAST didn’t load for a lot of time, I used NBCI BLAST tool. I took the quaries that their E value is 0, and have 95-100% identity. So there are 9 of them.