3DMD Jmol Tutorial: Basic Principles of Chemistry that Drive Protein Folding

Basic Principles of Chemistry that Drive Protein Folding

Proteins are large molecules that are synthesized in the polar, watery environment of the cell. They are made by joining amino acids together in a particular sequence. Because each of the 20 amino acids is different in shape and chemical property, proteins fold up into different three-dimensional shapes following basic principles of chemistry.

The Amino Acid Starter Kit introduced you to several of these basic principles of chemistry. This Jmol tutorial will allow you to determine how accurately a real protein, ß-globin, reflects these concepts in its final, folded structure.

The ß-globin protein. ß-globin is first shown here in a backbone format, and then later in an all-atom spacefilled format. The CPK coloring scheme is applied to the spacefilled model (carbon is gray, oxygen is red, nitrogen is blue, and sulfur is yellow).

The first chemistry concept that drives protein folding suggests that hydrophobic amino acids should be buried inside the protein while polar and charged amino acids should be on the surface of the folded protein where they are exposed to water.

To determine how well ß-globin reflects this concept examine the images generated by the buttons below:

Color Hydrophobic Amino Acids Yellow

Color Polar and Charged Amino Acids Red

Notice that proteins are a lot like students: they don’t follow all of the rules all of the time. Can you see examples of hydrophobic amino acids that are exposed on the surface of ß-globin?

To get a closer look at the inside of the protein, proceed to the next button.

Slab the Protein -- cut away the front of the protein to see which amino acids are buried in the core of the protein. To change the slab depth, hold the Ctrl and Shift keys and drag up and down using the left mouse button.

The CPK-colored molecule that is buried in the ß-globin is known as the "heme group". The orange-colored atom in its center is iron (Fe) and binds to oxygen gas (O₂). What is the function of the ß-globin protein?

So, based on your analysis of the images of ß-globin generated by above buttons...

Question 1:
How well do you think ß-globin follows this first concept of chemistry: that the hydrophobic amino acids should be buried?

The second chemistry concept that drives protein folding suggests that charged amino acids will be on the surface of a globular protein and that positively-charged sidechains will often be paired with negatively-charged sidechains.

Examine the images generated by the following buttons to determine how well this principle is followed in ß-globin.

Reset ß-globin

Display ß-globin in a Backbone Format

Add the Sidechains of Negatively-Charged Amino Acids

Add the Sidechains of Positively-Charged Amino Acids

Question 2:
Are the sidechains of the charged amino acids exposed on the surface of ß-globin?

Rotate this final image to examine closely how the positively- and negatively-charged amino acid sidechains are positioned in this protein.

Question 3:
Are the negatively-charged sidechains paired up with positively-charged sidechains?

In summary, while both of these basic principles of chemistry are reflected in the final folded shape of ß-globin, there are exceptions. Often the exceptions are important and suggest something about the function of the protein.

Now go to the second part of this Jmol Tutorial and examine five other proteins to see how well they reflect these basic principles of chemistry.