Modeling Biological Molecules
Today you will be working with the following files:
glucose.pdb
sucrose.pdb
amylose.pdb
stearic acid.pdb
oleic acid.pdb
glycerol.pdb
triglyceride.pdb
alanine.pdb
serine.pdb
leucine.pb
phenylalanine.pdb
peroxidase.pdb
collagen.pdb
deoxyribose.pdb
thymine.pdb
ATP.pdb
DNA.pdb
****Please note that on these models all the hydrogens are not always shown!!!
1. Water
During this lab you will look at 20 other molecules and answer questions about their structure, shape and
solubility. This is a compare and contrast exercise to help you reorganize different classes of molecules,
functional groups, monomers, polymers, molecular shapes, and hydrophobic and hydrophilic
characteristics.

Record the color of the elements represented by different colored balls.
2. Carbohydrates
 Monosaccharide
Open glucose.pdb. Change the settings on the screen to Ball and Stick Display. Practice moving, rotating
and increasing the size of the molecule.

Record the color of the elements represented by different colored balls.

What chemical elements are found in glucose?
1


Draw glucose in 2 dimensions below.
Calculate the molecular weight (mass) of glucose. You will use this mass in comparison through-out
the activity, so make note of it.

What functional group is common in carbohydrates? __________
Hydroxyl groups are polar functional groups. The oxygen tends to be negatively charged because of
electron clustering, and the hydrogens tend to be positive. As a result, a hydration shell can form around
the glucose molecule stabilized by H bonds. Thus, glucose interacts with water and dissolves in this
solution.

Predict whether glucose is hydrophilic or hydrophobic? Explain?
 Disaccharide
Sucrose (table sugar)
Open sucrose.pdb. and change to ball and stick display. Sucrose is isolated from plants for our
consumption (e.g. sugar beets; sugar cane). Plants transport sucrose made by the leaves via photosynthesis
to the roots for storage.


Compare the structures of sucrose to glucose. Explain your observations.
Add up the number of each type of atom in glucose and sucrose. Glucose____________,
Sucrose____________. How do you know these are carbiohydrates?
2

What are condensation and hydrolysis reactions?
Condensation reactions occur when a hydroxyl group of one sugar reacts with a hydroxyl group of another
to form a covalent bond called a glycosidic linkage by the removal of water from the structure. A
hydrolysis reaction can break bonds to yield (in this case) two monosaccharides. Condensation reactions
are used to form some molecule (not all) in organisms. Alternatively, a hydrolysis reaction is used to break
down some molecules.


On your model, locate the glycosidic linkage between the two sugars in sucrose.
Is sucrose hydrophilic or hydrophobic? Why? Is this prediction consistent with your
observations when you add sugar to your tea of coffee?
However, the large size of amylose causes the molecule to be only partially soluble in water. So like many
other molecules, amylose forms suspended aggregates in solution known as colloids. If a thousand glucose
units condense to form a starch molecule, what is the approximate molecular weight of the
starch?________
Close Sucrose and Amylose (leave Glucose open).
3. Lipids
 Saturated Fatty Acid
Open stearic acid.pdb under ball and stick.



What is a saturated vs. an unsaturated fatty acid?
Trace the carbon backbone on your computer screen. Calculate the molecular weight for stearic
acid.___________ Is this less than or greater than that of glucose? ______________
How would you describe the shape of stearic acid? How does the shape differ from that of
glucose?
3

What functional group is present in stearic acid?

Do you see any regions of the molecule that could be polar? _______
 Unsaturated Fatty Acid.
Open oleic acid.pdb and display it as ball and stick.

Compare and contrast the structures of oleric acid to stearic acid.
Oleic acid is an unsaturated fatty acid. It has a double bond between two adjacent carbons.

Draw a molecule comprised only of carbon and hydrogen with a double bond between 2 carbons
(Using the HONC 1234 rule).
The double bond causes the backbone to have a kink in it. The kinks prevent tight packing when in pure
state and this has implications about what its physical state will be. Unsaturated fatty acids tend to remain
fluid at temperatures that cause saturated fatty acids to solidify.
Close the fatty acid files.
 Glycerol.
Open glycerol.pdb as ball and stick display. Compare it to a carbohydrate, i.e., it is a polyhydroxyl
molecule.
Answer

List the number and type of atoms in glycerol.
4

Identify the functional groups in glycerol. Write their 2 dimensional structure below.
 Triglyceride
Ask your professor to draw a triglyceride on the board.
Carboxyl groups of fatty acids can undergo a condensation reaction with hydroxyl groups on other
molecule to form an ester linkage. Up to three fatty acids can be added to glycerol via its 3 hydroxyl
groups by forming ester linkages, forming a mono-, di-, or triglyceride. Different fatty acids can link with
each hydroxyl group to form a complex molecule. Sometimes fatty acids will link to two of the hydroxyls
and then a phosphate group will link to the third to form a phospholipid.


Draw the triglyeride your professor drew for you below. Circle the ester linkages located on the
molecule?
Do you think that a triglyceride would be hydrophilic or hydrophobic? Why?
Triglycerides and phospholipids are amphipathic molecules, large molecules that have both hydrophilic
and hydrophobic regions.
Note that types of fatty acids linked to each position of the glycerol in this model. In cells, the three fatty
acids could be the same or different. Sometimes they will have different backbone lengths or they will
have different degrees of saturation.

Which of the following do you think would form an oil at room temperature – a triglyceride
containing saturated fatty acids that all had backbones that were 18 to 20 carbons long or one
where the fatty acids were unsaturated with backbones of 14 to 16 carbons? Why?
Ask your professor to explain how lipids may pack according to their level of saturation.
5
 Phospholipids.
Ask your professor to draw a phospholipid.
Phospholipids are the types of lipids that are found in cell membranes. They are essentially a
diglyceride with a phosphate group on the third hydroxyl group of the glycerol.

Compare the structure of a fatty acid with a phospholipid.

How do phospholipids relate to the cell membrane? Why?

Are phospholipids hydrophilic/hydrophobic/amphipathic? (Circle one)
4. Proteins
Amino Acids
Open these four amino acid files as ball and stick display: alanine.pdb, serine.pdb, leucine.pdb, and
phenylalanine.pdb.

Draw the four amino acid structures in 2 dimensions from the 3D structure on the computer.

Draw the general structure of an amino acid.
6




Identify the four parts of an amino acid on your drawing.
Circle the R group on the four previous amino acid structures you have drawn.
Which of these four amino acids would you predict is hydrophilic? Why? Which is
hydrophobic?
What parts of an amino acid are shared among amino acids?
Peptides are short amino acid chains. Generally below 50 amino acids is considered to be a peptide.
Above 50 amino acids is usually referred to as a protein.
 Tripeptide.
Draw the synthesis of a tripeptide for yourself by drawing the condensation reaction between a single
amino acid and a short protein (peptide) that has two amino acids held together by a peptide bond (a
dipeptide).

How many peptide bonds are in a tripeptide? _______

Is a tripeptide a polymer? Y or N (Circle one)
7


True Proteins
Open peroxidase.pdb. and collagen.pdb. For this exercise you may want to change the types of display
models to answer the questions.

What is an enzyme?

Are all enzymes proteins?
Peroxidase is an enzyme. Its shape is globular, as are most enzymes. Ask your instructor what globular
means. Collagen is a structural protein and like most such proteins has an elongated shape. Collagens are
fibrous proteins found in connective tissue (tendons and ligaments). It also forms tough connecting sheets
that support our organs, is a component of bond and toughens the base of your skin.

Contrast the shapes of the two proteins.

Where do you find free amino or carboxyl groups in a protein? What are these two ends called?

How does the shape of peroxidase relate to its function as a catalyst?

How does the shape of collagen relate to its function?
 Enzyme Peroxidase
Enzymes have active sites where enzymatic reactions take place. RasMol has the ability to identify
structural features of peroxidase to show its active site. The active site of peroxidase contains a heme
group. This large group was synthesized from histamines (an amino acid) to form a prophyrin ring and can
conjugate tightly to an iron molecule. Peroxidases carry out reduction reactions in biochemical systems.
The iron serves as an electron carrier to assist this process. The active site of peroxidase is found deep in
the enzyme’s core to protect the iron from chemical reactions with water, which is a rich source of
electrons. This exercise will help you understand the role of polar (hydrophobic) and nonpolar
(hydrophilic) amino acids in protein folding. Without proper protein folding, proteins like peroxidase
would not function correctly.
8

What is a reduction reaction?

What is an oxidation reaction?
Polar amino acids are hydrophilic. To view the location of the polar amino acids in peroxidase, do the
following
1. Have the peroxidase file open and displaying in its window as a wireframe with a black
background.
2. Go to the top of the screen and click WINDOW to open the RasMol Command Line
screen (a white background screen) so that both windows are open.
3. Click on the Command Line box and type the following after the prompt: select polar.
Press the enter (return) key.
4. After the prompt type color green.
5. Go to the top of the screen and under DISPLAY choose Ball and Stick. All of the polar
amino acids in peroxidase should now be displayed in green as ball and stick models.

Rotate the molecule and decide whether there are any more polar amino acids to the outside of
the molecule than there are on the inside. What do you think? How does this relate to the shape
of the protein in aqueous solutions?
Confirm this observation by now visualizing where several nonpolar amino acids are located. Review the
amino acids and identify those that are nonpolar. Note the standard abbreviations for these amino acids.
Enter the standard abbreviations into RasMol by typing the following:
1. Select ala, val, leu, met, phe (return)
2. Color orange (return)
3. Go to the top of the screen and under DISPLAY choose Ball and Stick. All of the
nonpolar amino acids should now be shown in orange.

Rotate the molecule so that you have good viewing angles. Are most of the nonpolar amino acids
located on the outside of the protein or toward the inside? Why?
9
As you look inside the molecule, look for a polygonal structure. This is a heme group that marks the active
site. It is a non-amino structure that gives the enzyme its ability to break down hydrogen peroxide to water
and oxygen. To visualize the heme group, open the COMMAND WINDOW. Type the following:
1. Select hem (enter)
2. Color red (enter)
3. Go to DISPLAY at the top of the screen and click on Space Fill.
The active site should now be clearly visible. Rotate peroxidase and find the channel that allows hydrogen
peroxide (a substrate for peroxidase) to bind with the porphyrin ring.
 Go to FILE at the top of the screen and close the file. Reopen the peroxidase file so that you have a
fresh display of the original molecule. This time you will investigate where specific amino acids are
located in the protein.
There are several ways to do this. The first, although easy to perform, yields a complex picture. Go to
OPTIONS at the top of the screen and click on labels. The names of all of the amino acids in the primary
sequence from the amino terminal end. (Remember that every protein, regardless of how large, has a
carboxyl group on one end and an amino group on the other.) You can enlarge the view of the molecule by
going to the Command Line screen and typing zoom 200 (or some other number greater than 100). This
will help you see the labels.

What is the largest number that you can see? __________
If you have found the amino acid that is on the carboxyl terminus, you have identified the number of
amino acids in the protein. Go back to OPTIONS and click on labels again to turn them off.

Do amino acids that are distant from each other linearly come together to form a 3-D structure?
Now you will experiment at finding where in peroxidase different amino acids are located. Be sure that
you are starting with a wireframe display of peroxidase with the CPK color checked in the COLOURS
drop-down menu. Click on the Command Line screen and enter the following:
1. Select ala (or the standard abbreviation of any other amino acids that interest you
2. Go to the OPTIONS menu at the top of the screen and click on labels.
3. Go to the DISPLAY menu at the top of the screen and click on Ball and Stick.

You can now see where in the molecule alanine is located and the positions of this amino acid in
the primary structure. How many alanine residues are found in peroxidase?___________
Repeat this analysis for another amino acid.
Close the data file for peroxidase by going to FILE at the top of the screen and clicking on CLOSE.
10
4. Nucleic acids
 Nucleotides
Sugars in nucleotides are the basic subunits of DNA and RNA. Open deoxyribose.pdb as a ball and stick
display.

How is this molecule similar to glucose? How is it different?

Draw this structure in 2 dimensions below.

Nitrogenous bases in nucleotides.
Open thymine.pdb as a ball and stick model

Draw this structure in 2 dimensions below
11
 A complete nucleotide.
Adenosine triphosphate (ATP)
Open ATP.pdb. as a ball and stick display. ATP acts as an energy transfer molecule in most cellular
reactions and a derivative of it is found in RNA.


Draw the structure in 2 dimensions below.
Identify the nitrogenous base, sugar, and phosphate group in the molecule. Look again at the
sugar. Is it ribose or deoxyribose? _________________
 DNA (Deoxyribose Nucleic Acid).
Open DNA.pdb as a ball and stick model. This is just a short sequence of a DNA double helix. DNA
isolated from a human chromosome would be thousands of times longer. Nucleotides can chemically join
together in condensation reactions to form phospodiester linkages between the nucleotides.

Look carefully at the DNA double helix and identify where the nitrogenous base portion of each
nucleotide is located. Where are the sugar and phosphate portions of each molecule located?
The bases projecting to the inside of the double helix form hydrogen bonds with each other. It is these
hydrogen bonds that hold together each of the single helices in a double helix. Go to WINDOW at the top
of the screen and click on COMMAND LINE. A new box will appear. After the prompt, type hbonds on.
The program will now draw the hydrogen bonds in as dashed lines. Rotate the molecule so that you can
see them.

What are the basic base pairing rules of DNA and RNA?
12