Week 4 HW: Protein Design Part I
Objective:
Learn basic concepts:
- amino acid structure
- 3D protein visualization
- the variety of ML-based design tools
- Brainstorm as a group how to apply these tools to engineer a better bacteriophage (setting the stage for the final project).
Part A. Conceptual Questions
Answer any NINE of the following questions from Shuguang Zhang: (i.e. you can select two to skip)
1. Why do humans eat beef but do not become a cow, eat fish but do not become fish?
2. Why are there only 20 natural amino acids?
3. Can you make other non-natural amino acids? Design some new amino acids.
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
In this section, we will learn about the capabilities of modern protein AI models and test some of them in your chosen protein. We will now try multiple things in the three sections below; report each of these results in your homework writeup on your HTGAA website: