Part A: Something to Ponder

1. Answer any of the following questions by Shuguang Zhang (pick your favorites!):

• 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)
  • About 5819.5 kilodalton
• Why humans eat beef but do not become a cow, eat fish but do not become fish?
  • Because a cell by itself doesn’t have so much of an identity. It gets its identity by being part of a bigger cell collective or tissue. When the cell loses its “context” (e.g. a piece of beef being cut away from the cow) it no longer acts as part of the global context of the cow. As soon as it enters our bodies, the digestion system secretes the beef tissues and extracts only what is useful for it.
  • That being said, this is a very interesting area of research that is currently being studied by M. Levin’s Lab at Tufts University: why is there anything but cancer? In cancer, a cell leaves the collective and starts “pursuing” its own (selfish) goals. But why is that not the default? How does it ever happen that groups of cells come together and act in harmony?
• Why there are only 20 natural amino acids?
  • There are some hypotheses:
    • First to come: these 20, generally simple and readily available, amino acids were the first to be press-ganged into life
    • “frozen-accident theory”: they’re arbitrary, a different group of 20 would be just as good
    • Protein Formation: Forming soluble, stable protein structures with close‐packed cores and ordered binding pockets needed the variety of amino acids we see today
    • Mapping chemical space: the set that is used by biology has a number of surprisingly non-random properties that stand out very clearly → just abo ut every test you can throw at them says they are non-random – not only do they cover a good range but they are not clumped to extremes
    • Oxygen: a 13 amino acid alphabet can create folded, soluble, stable and catalytically active ‘proteins’, albeit not as active or stable as the parent proteins on which they were based → molecular oxygen forced life to incorporate the last six novel amino acids
    • tRNA limitation: the problem is finding ways to make new tRNA molecules that could recognise a new amino acid without picking up existing ones
    • Arguing against the “clean” chemical theories: The chances are it was once much messier, with many different types of molecules and mechanisms involved that may have now been replaced
• 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?
  • The Miller-Urey experiment showed that with just water, ammonia, hydrogen and methane – and electric sparks to mimic lightning – you could form several of the protein precursors necessary for life on Earth
• If you make an alpha-helix using D-amino acids, what handedness (right or left) would you expect?
  • Right-handed; left-handedness is very rare
• Can you discover additional helices in proteins?
  • Yes, there are other helices, such as the 3_10 helix and π helix, though they are rarely observed in natural proteins except at the ends of α helices due to unfavorable backbone packing in the center of the helix (source: https://en.wikipedia.org/wiki/Protein_secondary_structure#Types)
• Why are most molecular helices right-handed?
  • We don’t know. It’s an interesting feature of life on earth that most molecules are right-handed. There are left-handed molecules, they just don’t occur in natural life forms.
• Why do beta-sheets tend to aggregate? What is the driving force for b-sheet aggregation?
  • beta-sheets form hydrogen bond networks with their neighbors in which the N−H groups in the backbone of one strand establish hydrogen bonds with the C=O groups in the backbone of the adjacent strands (source: https://en.wikipedia.org/wiki/Beta_sheet#Geometry)
• Why do many amyloid diseases form b-sheet?
  • Can you use amyloid b-sheets as materials?
• Design a b-sheet motif that forms a well-ordered structure.

Part B: Protein Analysis & Visualization

In this part of the homework, you will be using online resources and 3D visualization software to answer questions about proteins.

An interactive version of my analysis is available here:

https://ricomnl.github.io/protein_structure_analysis/notebooks/analysis.html