Week 1 HW: Principles and Practices
Conceptual question
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)
Meat is primarily composed of approximately 75% water, 19% protein, and 5% fat, along with small amounts of minerals and carbohydrates. 500 less or more 100g of protein (100g / 1.66×10−24 )/100 = 6.0×1023
Why do humans eat beef but do not become a cow, eat fish but do not become fish?
Enzime breaks cow or fish proteins into amino acids, fats into fatty acids, and nucleic acids into small components. Then your own cells rebuild human molecules from those parts according to the human genome and human regulatory patterns
Why are there only 20 natural amino acids?
enough chemical diversity to build stable, functional proteins, but not so many building blocks that translation machinery becomes much harder to evolve and maintain
Can you make other non-natural amino acids? Design some new amino acids.
They can be added chemically during peptide synthesis or genetically encoded using engineered tRNA/aminoacyl-tRNA synthetase systems.
Where did amino acids come from before enzymes that make them, and before life started?
Before enzymes and life, amino acids were synthesized via non-biological (abiotic) processes, likely arising from atmospheric chemical reactions, hydrothermal vents, or extraterrestrial impacts. Simple compounds like methane, ammonia, and cyanide combined using energy sources like lightning, ultraviolet light, or heat to produce these building blocks, creating a “primordial soup”.
If you make an α-helix using D-amino acids, what handedness (right or left) would you expect?
right-handed α-helices are favored because proteins are built almost entirely from L-amino acids.
Can you discover additional helices in proteins?
Many theoretically possible helices are unstable or transient, which is why only a few are commonly observed.
Why do β-sheets tend to aggregate?
β-strands expose backbone hydrogen-bonding groups that can easily form intermolecular interactions.
What is the driving force for β-sheet aggregation?
Hdrogen bonding Hydrophobic interactions (exclusion of water) and tight side-chain packing (dry, low-energy interfaces)
Why do many amyloid diseases form β-sheets?
When normal protein folding or clearance fails, proteins can misfold into β-rich structures that self-assemble into fibrils, which are often toxic and accumulate in tissues.
Can you use amyloid β-sheets as materials
Yes bc they are ordinate and resistent
Analyzing protein
Deep Mutational Scans
the blu line convy the importance of that aminoacid. I sprobabily a binding site or have idrophobicity
Latent Space Analysis
Similar protein with gradual change, no group detected
Folding
Depend on the site the resistace to mutation
Inverse-Folding a protein
Nope not close many mutation
Engeneer
Our group plans to computationally engineer the ΦX174 L lysis protein for increased stability. We will use protein language models for mutational scanning, conservation analysis to avoid critical residues, structure prediction to check fold preservation, and stability prediction tools to rank candidate mutations. Our hypothesis is that a more stable L protein may function more reliably and potentially improve phage performance. The main risk is that computational stability does not necessarily translate to improved biological activity.