Week 4 HW: Protein Design Part I

Part A. Conceptual Questions

Answer any NINE of the following questions from Shuguang Zhang: (i.e. you can select two to skip)

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

Part B: Protein Analysis and Visualization

In this part of the homework, you will be using online resources and 3D visualization software to answer questions about proteins. Pick any protein (from any organism) of your interest that has a 3D structure and answer the following questions:

  Briefly describe the protein you selected and why you selected it.
  Identify the amino acid sequence of your protein.
  How long is it? What is the most frequent amino acid? You can use this Colab notebook to count the frequency of amino acids.
  How many protein sequence homologs are there for your protein? Hint: Use Uniprot’s BLAST tool to search for homologs.
  Does your protein belong to any protein family?
  Identify the structure page of your protein in RCSB
  When was the structure solved? Is it a good quality structure? Good quality structure is the one with good resolution. Smaller the better (Resolution: 2.70 Å)
  Are there any other molecules in the solved structure apart from protein?
  Does your protein belong to any structure classification family?
  Open the structure of your protein in any 3D molecule visualization software:
  PyMol Tutorial Here (hint: ChatGPT is good at PyMol commands)
  Visualize the protein as “cartoon”, “ribbon” and “ball and stick”.
  Color the protein by secondary structure. Does it have more helices or sheets?
  Color the protein by residue type. What can you tell about the distribution of hydrophobic vs hydrophilic residues?
  Visualize the surface of the protein. Does it have any “holes” (aka binding pockets)?

Part C. Using ML-Based Protein Design Tools