Appreciating the Diversity of Primary Sequences in Protein Structure

Written by Kelly A. Hogan, University of North Carolina at Chapel Hill

Learning Outcomes:

– To gain an appreciation for the diversity of proteins in amino acid sequence and length

– To examine an internet tool utilized by research scientists

– To appreciate quantitative biology

Activity Description: A classroom demonstration involving one student and multiple pairs of mittens of different colors is used as an analogy to the 20 amino acids that can be ordered in a multitude of ways in primary protein structure. Students can then use theNationalCenter for Biotechnology Information (NCBI) website to explore real proteins.

Time Needed: The activity should take approximately 15 minutes

Materials Needed: Multiple pairs of mittens or gloves

Activity Instructions:

One student comes to the front of the room in which there are two pairs of mittens (say a red and a blue pair). The student is allowed to choose one for each hand. Ask the audience, “How many possible combinations are there?” (Answer: 4)

Students won’t need a mathematical equation to figure this out:

Right – red, Left – red or Right – red, Left – blue or Right – blue, Left – blue or Right – blue, Left –red

Next put another pair of mittens on the table for your student to choose from (there are three pairs total at this point). Ask the audience, “How many combinations are now possible?” (Some students may start forming combinations of colors. Give them time to see how difficult this can be. Others may see the need for a calculation more quickly.) This is a good time to point out that biology is quantitative (many students will not recognize at the introductory level that as biology advances it intersects with mathematics more and more.)

The equation for the two hands and three pairs of gloves is: 32 = 9

Two hands and four pairs of gloves: 42 = 16

Next ask the audience, “How many amino acids exist?” (Answer: 20). Make the analogy clear by explaining that you could bring 20 pairs of mittens to your student. And ask them, “For a dipeptide sequence, how many different combinations would be possible?” (Answer: 202 = 400).

(Be sure to note that Ala-Leu is indeed different from Leu- Ala because polypeptides have directionality with an amino end and a carboxyl end.)

Lastly, ask students how long a typical polypeptide is. Let them take guesses and then explain the variation that exists. You can let them name a few proteins they know and go to:

http://www.ncbi.nlm.nih.gov/protein

to show them how many amino acids are in their named proteins. (This is a great site to show them as a collaborative tool that scientists use in the research.)

Ask them to calculate the number of combinations in a protein with say 125 amino acids:

Answer:  20125 = 4.25352959 × 10162

Note: You can bring in this same idea again when you discuss the triplet nature of the DNA code. With 4 nucleotides and a triplet sequence there are 43 = 64 combinations or codons.