In the first part of this tutorial you identified the nucleotide and, subsequently, the amino acid that are affected by the sickle cell anemia mutation. Now you are going to use a program called “Jmol” to visualize the wild-type and mutant hemoglobin proteins. Jmol will allow you to view the proteins in 3 dimensions, and will also show you where the mutation that causes sickle cell anemia occurs in the folded hemoglobin molecule. In addition, you will see how this mutation causes hemoglobin molecules to clump together.

The two protein sequences that we are going to use are as follows:
1hab = normal hemoglobin (wild-type) with no mutations
2hbs = mutated hemoglobin that causes Sickle Cell Anemia

With the use of Jmol, we will be able to view the structures of the two hemoglobins side-by-side. This will make the comparison of the two much easier.

Why does the single amino acid cause two hemoglobin molecules to stick together? The problem arises because valine is a non-polar amino acid whereas glutamic acid is polar. Basically what this means is that valine does not like to be in contact with water. How do non-polar amino acids cope in our cells which are three-quarters water? To “hide” from water, non-polar amino acids such as valine tend to clump together (that way at least some of their surface area is not exposed). When mutant hemoglobin molecules with non-polar valines contact one another, the valines stick together. When oxygen is abundant, the clumped hemoglobin molecules do not cause a problem, but when oxygen levels fall (for example, in working muscle cells), the clumped hemoglobin molecules have a tendency to precipitate causing the red blood cells to collapse into the shape of a sickle with jagged corners. The sickled red blood cells tend to block narrow blood capillaries resulting in severe pain and tissue damage.

Click to start the viewer. In order to use the viewer, you will need Java which can be downloaded from