Protein Folding Exercise
Proteins are macromolecules made up of long chains of amino acids joined by peptide bonds that form complex
folded structures. Proteins are responsible for numerous functions including structure, storage, hormones,
enzymes, antibodies, transport of molecules (such as in membranes, or hemoglobin), and receptors. A protein’s 3D
structure is determined by the interactions of its side chins on the amino acids that make it up. This structure
determines how a protein functions and interacts with other molecules in the body. The human genome contains
information for the construction of over 20,000 different proteins!
Amino Acid R group color code
Blue: basic (positively charged)
Red: acidic (negatively charged)
Yellow: non-polar
White: polar
Green: cysteine
Directions:
1. Randomly distribute the beads (amino acids) along your pipe cleaner. Evenly space the beads along the
entire length.
 What level of protein structure is demonstrated by the order of the amino acids?
 What type of bond is holding this level of structure?
2. The first three amino acids form an alpha helix. Curl the pipe cleaner around a pen to create a helix shape
along the pipe cleaner for the first three beads.
 What level of protein structure is demonstrated by a repeated shape (an alpha helix or beta
sheet)?
 What type of bond is holding this level of structure?
3. Follow the indicated rules about how different side chains of different amino acids interact to fold your
protein further.
Protein Folding Rules
I.
II.
III.
If the environment for this protein is inside of a cell, think about where the polar vs. non-polar amino
acids will arrange as the protein folds. Which will tend to be on the outside of the protein vs. which
will tend to be on the inside?
Charged side chains will tend to form an ionic bond with a side chain from an amino acid with the
opposite charge.
Cysteine side chains (green) often interact with each other to form covalent disulfide bonds that
stabilize protein structure.
4. Have the four polypeptides created by your group interact trying still to obey the rules of side group
interactions.
 What level of protein structure is demonstrated by the joining of several polypeptide
subunits?
Post Lab Discussion Questions:
1. Compare the proteins. All bags contained different amino acids. What do you notice about the 3D
protein structures?
2. What happens if you unfold a protein and refold it?
3. What types of things can denature proteins?
4. What will happen to your protein if one amino acid changes from yellow to white? How might this affect
the proteins functionality?
5. What determines the order of amino acids in a particular protein?
6. Where in a cell does protein construction take place?