Protein Folding


Activity 1

Follow the steps below and answer the question that follows

    • Choose “hydrophobicity” as the color scheme
    • Select “water” as the solvent type
    • Click “play”
    • Observe how the polypeptide reacts
    • After a moment, click “generate random protein” to produce a new polypeptide
    • Click “play” to observe the reaction of the new polypeptide
    • Repeat this process again for a total of three observations

Question 1: How does the polypeptide behave in an aqueous (water) environment? How do hydrophobic and hydrophilic amino acids behave differently?

Activity 2

Follow the steps below and answer the question that follows

    • Click “generate random protein” to reset the polypeptide
    • Repeat the steps from Activity 1, but choose “oil” as the solvent type

Question 2: How do the amino acids arrange differently when the polypeptide is allowed to fold in oil as opposed to water?

Activity 3

Many molecular interactions influence how polypeptides conform (fold) into their final shape. You have observed how water and oil influence conformation. Now you will view how the polypeptide behaves if in a vacuum. This will allow you to see how intramolecular interactions between amino acids influence protein conformation.

    • Click “generate random protein” to reset the polypeptide
    • Select “charge” as the amino acid color scheme
    • Choose “vacuum” as the solvent type (this will eliminate hydrophobic and hydrophilic interactions)
    • Click “All hydrophilic” to include only charged and polar amino acids in your polypeptide (positively charged amino acids are blue, negatively charged amino acids are red, and polar amino acids are gray)
    • Click “play” and observe how the polypeptide behaves
    • After a few moments, click “All hydrophilic” again to re-arrange the amino acids
    • Continue to observe how the amino acids react toward one another


Question 3: What pattern of interaction do you observe between the amino acids? Keep in mind that adjacent amino acids are connected by strong covalent peptide bonds.  Consider the interactions that occur between amino acids that do not share a peptide bond.


This simulation will help you see how a polypeptide chain folds in various solvents. Hydrophobic amino acids are golden orange. Hydrophilic amino acids are green.


The image above provides a visual representation of the four levels of protein structure.  Hydrophobic interactions are very influential in determining a protein’s tertiary structure.

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Polypeptides and Water

The simulation above represents an amino acid (polypeptide) chain. Certain properties are used to characterize amino acids. For example, some amino acids are attracted to water (hydrophilic), while some amino acids are repelled by water (hydrophobic). This attraction and repulsion has to do with hydrogen bonds. Amino acids that are electrically charged (positive or negative), and amino acids that are polar (regions of partial charge), are hydrophilic. Amino acids that are non-polar, meaning they have a balanced electrical charge, do not form hydrogen bonds with water and disrupt existing hydrogen bonds between water molecules. As a result, non-polar molecules are driven to re-arrange themselves to minimize the amount of their surface area that comes into contact with water. Non-polar amino acids are hydrophobic.

The video above comes from article: Cutting a Drop of Water Pinned by Wire Loops Using a Superhydrophobic Surface and Knife, published in the journal PLOS ONE. The video is a neat illustration of how water behaves when in contact with a hydrophobic surface.


Looking for more biochemistry review activities?  Click the button below.

Biochemistry Review: Hydrogen Bonds and Polar Molecules

1 Comment

  1. This website really did help me understand the concept of proteins. I am so comfortable and i could totally explain this to someone if they asked.


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