Download Computers, Chemistry, and Biology in a First Year Seminar

Computers, Chemistry, and
Biology in a First Year Seminar
Julie B. Ealy
Assistant Professor of Chemistry
Pennsylvania State University
Lehigh Valley
American Chemical Society
August 2005 Washington, DC
First Year Seminar at PSU
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Required of all freshman
Skill development
Academic integrity
Sense of community
Active and collaborative learning
Technology
• 8 months in preparation
Molecular Modeling – Spartan Pro
– utilize computer generated software that permits
3D visualization of molecular images that
enhances understanding of molecular structure
• Organic bases of RNA – 3D structure, formula,
hydrogen bonds
• 20 amino bases – name, abbreviation
• 21 nucleotides of cDNA for the spike glycoprotein
of SARS – identify complementary RNA – aa
• Build a beta sheet – 3 amino acids
• Build an alpha helix – 8 amino acids
Atoms, Formulas, Bonds
Guanine - Cytosine
Hydrogen bonds, Formula
Amino Acids
Below are the twenty amino acids. Amino acids are the monomer building
blocks of proteins.
1) Fill in the name of the amino acid in the space below the amino acid,
followed by the three-letter amino acid abbreviation, then the one letter
symbol. (These are found on p.7 of this exercise.)
2) Write the formula in the second space beneath the name as you view the
molecule from left to right. An example of the first one would be:
occhnhch2oh. The order could be somewhat different than written. If you are
unsure about the identity of an element, look at the amino acid molecule in
the window displayed at the right in Spartan Pro.
Beta Sheet
In Spartan Pro choose file, new, and peptide (on the right). Make sure
that  (beta) sheet is checked near the bottom right. Choose any amino
acid and click on the screen. Orient the amino acid so the N-H (amine
group) of the amino acid is on the left. The C=O (carbonyl) group should
be on the right. Choose another different amino acid. Click on the end
of the yellow hydrogen of the carbonyl group of the amino acid on the
screen. Choose a third different amino acid. Click on the yellow
hydrogen bond of the 2nd amino acid. There should now be three
amino acids on the screen.
Carbonyl and Amine Groups, Peptide bonds and Unit
Red – Circle the carbonyl groups
How many carbonyl groups?
Blue – Circle the amine groups
How many amine groups?
Green – Circle the side chains of the amino acids.
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Use the figure in this section as a guideline and draw an arrow to the peptide bonds on your
polypeptide. How many peptide bonds are there?
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Draw a “square” around one peptide unit on you polypeptide.
In the first part of this section a  (beta) sheet was chosen to build polypeptide. The beta
strand on the screen represents the secondary structure of a polypeptide.
Alpha Helix
In Spartan Pro, choose new, peptide,  helix. Choose 8 different amino acids
(except glycine) always joining the amino acid to the hydrogen of the carbonyl
group. The polypeptide will need to be rotated to find the hydrogen. Rotate the
alpha helix until you can “see” down through the middle. Choose Build, minimize.
The polypeptide chain will move and an energy value will be reported on the
lower right corner of the screen. When you chose “minimize” the polypeptide
moved and tweaked and settled into a more stable arrangement. The lower an
energy value is, the more stable the structure.
Main Proteinase of SARS
Magnified View of Main Proteinase with Residues
Use the “magnifier” icon to make the protein bigger so you can see the amino acid letter
and number better. Rotate the protein and identify four amino acids in different locations.
Fill in the blanks with the letter abbreviation and amino acid number. Write out the
complete name of the amino acid, also.
Interactive Docking with Streptavidin and Biotin
What is seen on the screen is streptavidin, a bacterial protein, complexed with
biotin (purple), a ligand (which in this case is a fancy name for a molecule). The
structure of the complex was determined in 1989 by Weber, et al. Biotin is actually
vitamin H and is necessary for metabolism and growth in humans. Biotin binds
tightly to streptavidin and makes the complex one of interest in research. If the
binding of biotin to streptavidin can be understood better, it will aid in the design of
new drugs and ligands for proteins and nucleic acids.
Identification of a Binding Site for a Drug
What has happened is that a potential binding site for a ligand has been identified.
If this was a different protein several potential binding sites would result. Click on
the square to the left of g_pocket 1 to make the square blue. The binding site that
has been identified is the approximate location that biotin binds to streptavidin.
Identification of Neighboring Atoms around the Biotin
The neighboring atoms around the pocket define where biotin will dock itself. The
green crosses that are displayed define the pocket.
The Pocket for Biotin
The amino acids (in yellow) define the space around the pocket where biotin will fit.
Biotin Docked into the Defined Pocket
The ligand, biotin, samples the defined space to find the lowest and most stable
energy configuration in conjunction with the protein, streptavidin.
Energy Values Sampled by Biotin
The plot is all the energy values that resulted as biotin sampled the space that was
defined by the amino acids - the neighboring atoms - of streptavidin. The lowest and
most stable energy value is found at, -56.8. In the tutorial on amino acids and
secondary structures – alpha helices and beta sheets – were minimized. The
structures “tweeked” as they achieved the most stable configuration and repulsive
interactions were minimized. An energy value resulted after the minimization.
What Did Students Say about the Computer
Technology?
The thing that astonished me was that there are approximately 1256 amino
acids that make up the spike glycoprotein. Now that I have seen what a
single amino looked like, then to think of 1256 of them all linked to each other
(for the SARS spike glycoprotein) is amazing.
 The Spartan Pro program is a great tool to generate a visual aid as a
backup to what we are discussing in class. Because my science background
is limited, comprehension of structures is difficult without a picture as
reinforcement.
 The” fieldtrips” to the chemistry labs were nice in that it allowed us to
visualize and manipulate many of the chemical aspects of diseases and
drugs.
 The thing that most impressed me was the programs we got to use to
visualize the virus and the amino acids.
Acknowledgements
• Adrienne Dorward – Penn State student
• Penn State University, Lehigh Valley
Research Development grant