Stony Brook University
Protein Modeling Challenge
February 28, 2014
Fall 2014
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SIZE
RESTRICTION
The finished model must fit into a box that is
44cm x 28cm x 21cm.
You may bring additional display materials with
you on the day of the competition.
Electricity will not be available –sorry- I know it
would be cool since Ras is a switch
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Location
• Registration in SAC Ballroom A
• Testing and Model Building on the 3rd floor of
the SAC
• The Scientists want to CHAT with your
students - so after the exam and model
building the students will display their
prebuilt models in SAC Ballroom A. They will
stand by their model ready to discuss and
explain it. This interlude will not be judged.
– Your students may bring handouts or whatever to
show during the chat session
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Joan Kiely, Stony Brook University
[email protected]
Debbie Pelio, Stony Brook University
[email protected]
http://www.stonybrook.edu/cesame
Linda Padwa, Stony Brook University
Kristen La Magna, Stony Brook University
Shannon Colton, Ph.D., Technical Advisor
Milwaukee School of Engineering
http://cbm.msoe.edu/
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Protein Modeling Challenge
• To compete successfully in the Protein
Modeling Challenge, you will:
– Learn the AMAZING fact that enzymes
can act like little timers cells
– Build models that illustrate what you know
about Ras.
– Become a maven of protein structure
– Enhance your computer skills with Jmol
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Useful Web sites
• Protein Data Bank
http://www.pdb.org/pdb/home/home.do
• Center for Biomolecular Modeling
http://cbm.msoe.edu/
• Tutorial for using jmol note that the Protein
Challenge is not exactly like the Science
Olympiad so the tutorial is not an exact match
• CBM jmol resources
http://cbm.msoe.edu/stupro/smart/resources
.html, you can download jmol from this site.
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Web-Based Resources
•
This powerpoint presentation will serve as an interactive resource
for your team to gain the knowledge they need to be successful in
the Protein Modeling Challenge
•
You will find links distributed throughout this presentation,
indicated by the blue underlined text
•
Follow these links to the appropriate sources
•
Good luck and have fun!
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Resources for Ras
•
Goodsell, Ras Protein Molecule of the Month April 2012, Protein DataBank,
http://www.pdb.org/pdb/101/motm.do?momID=148
•
Pai, E.F., Krengel, U., Petsko, G.A., Goody, R.S., Kabsch, W., Wittinghofer, A. Refined
crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution:
implications for the mechanism of GTP hydrolysis. PubMedCentral: PMC552258
–
•
•
RESEARCH ARTICLES FREE THROUGH PUBMED CENTRAL http://www.ncbi.nlm.nih.gov/pmc/
Alfred Wittinghofer, iBiology Seminars, available on YouTube®
–
Part 1 GTP Binding Proteins as Molecular Switches, the students will find the whole
video useful.
–
Part 2 GTPase Reactions and Diseases, the sections from 1 to 19:20 minutes will be
useful and the information listed on the slide “Conclusion 1”. The later parts may be
engaging for those interested in disease but could easily be overwhelming. They are not
responsible for information from the section on aluminum fluoride, the other Ras type
proteins or information listed under “Conclusion 2”.
–
Notice that Professor Wittinghofer is one of the authors of PDB file 5P21. He is listed
as the final author on the accompanying paper; this placement tells us that he was one
of the primary intellectual contributors.
Campbell and Reece, Biology, or similar introductory biology textbook chapters on cell
communication and intracellular signaling cascades, I will use Campbell text and figures for
creating questions.
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Resources for Ras
•
Proteopedia article on Ras:
– http://www.proteopedia.org/wiki/index.php/User:Joseph_Lipsick/RAS
– http://www.proteopedia.org/wiki/index.php/Ras is the open-edit version and so may
have some errors.
– ***Note that the article on Allosteric Modulation was written by someone that is
confused about the conclusions of a paper. Students should read this section only with
supervision; for example calcium acetate would dissociate to Ca++ and acetate- in the
cytoplasm. The scientist used an observation of the crystal structure to create a
mental model of what is happening in the cell. They did not say that acetate affects
Ras in cells. The reference article is free and linked to the proteopedia page.
http://www.proteopedia.org/wiki/index.php/Allosteric_modulation_of_H-Ras_GTPase.
COULD BE A TEACHING MOMENT FOR YOU 
•
Feldber, R, Structural Aspects of ras Protein Tutorial, Dept. of Biology, Tufts University
http://ase.tufts.edu/biology/MolecVisual/bio152/rightrasD.html
•
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Protein Structure
Resources
•
The following links will serve as tools
to help you learn the basic information
needed to be successful in this
challenge. Please follow these links:
Basic Introduction to Protein Structure and
Modeling
•
•
http://cbm.msoe.edu/teachRes/index.html go to the
bottom of the page for links
•
http://cbm.msoe.edu/stupro/so/index.html
Protein Databank and The Protein
Databank Molecule of the Month,
www.pdb.org
•
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Protein Structure
•
•
•
Proteins are macromolecules
Amino acids are the basic building blocks of proteins
Working as a team, make an amino acid
Sidechain (R-Group)
Alpha-Carbon
Carboxyl
Group
Nitrogen
Amino Group
•
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is your amino acid L or D form?
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D-Alanine
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L-Alanine
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Amino Acids Have Unique
Chemical Characteristics
•
Each amino acid has the same “backbone” structure, but has
different chemical groups (R groups or sidechains) attached
•
Working with another team, construct an amino acid and a
dipeptide with a molymod kit
NH2-CH-COOH
R
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Proteins Have Secondary
Structure
•
A linear chain of amino acids is the
protein “primary” structure
•
A chain of amino acids will
spontaneously form stable
“secondary structures”, ie: betasheet or alpha-helix
•
•
Hydrogen bonds may stabilize these
structures
Science researchers would like to
understand what controls this
folding.
Alpha Helix
Beta-sheet
– http://fold.it/portal/
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Proteins Fold Into a Tertiary
Structure
•
Protein folding is due to the behavior of different chemical
groups on amino acids in an aqueous environment
Structural Biologists and Computer Scientists are collaborating
improve our ability to predict protein structure and better
understand MOTIFS and DOMAINS in proteins
You can explore amino acid
sidechain chemistry and protein
structure through the game and
programs at:
Fold It: http://fold.it/portal/
or
Rosetta@Home
http://boinc.bakerlab.org/
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Proteins Fold Into a Tertiary
Structure
•
Proteins spontaneously fold into a specific three dimensional
“tertiary” structure that governs a protein’s function
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Protein Data Bank
•
The 3-dimensional structure of proteins is often determined
by x-ray diffraction or NMR analysis
•
PDB file lists the X, Y, Z coordinates for each atom in a
protein
•
Protein Data Bank http://www.pdb.org/pdb/home/home.do
•
PDB Molecule of the Month features the structure and
function of a different protein
each month
http://www.pdb.org/pdb/static.do?p=education_discussion/
molecule_of_the_month/alphabetical_list.html
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Molecule of the Month (MOM)
•
A monthly PDB feature written by David Goodsell
http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_m
onth/alphabetical_list.html
–
Features a specific molecule
–
Describes protein function
–
Relates structure with function
This figure is a science-artist’s
interpretation of a tyrosine kinase
receptor (an activator of Ras)
The image is based on biochemical,
genetic and structural (NMR and
crystallography) data. Notice how
many types of scientist were
involved.
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•
•
•
Jmol
Jmol is a computer visualization software that displays data
from a PDB file as a “3D” image of the molecule on the
computer screen
Jmol is Java-based and will work on most computers
http://cbm.msoe.edu/teachRes/jmol/index.html
–
•
•
http://jmol.sourceforge.net/ has jmol for downloading and
userguides.
http://bioportal.weizmann.ac.il/oca-docs/fgij/index.htm
–
•
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Be sure that you know how to use the downloaded version before the
day of the competition. Also be sure that you can use the console
display.
Note that this version of jmol is easier to use but is not the interface
the students will use at the competition.
Your students should practice using the console and a
downloaded version!
We will be using version 13.0
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Exploring Protein Structure
with Jmol
•
Jmol allows you to identify elements of protein structure
–
Helix (magenta)
–
Sheet (yellow)
–
N-terminus (blue)
–
C-terminus (red)
–
Amino acid sidechains (CPK)
–
Alpha-carbon backbone model format
–
Spacefill to get a sense of the volume
–
Surface view to give a holistic view of the protein
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Mini-Toober Models (cont.)
•
Mark location of structures on Mini-Toober
•
Fold Mini-Toober into a 3D model representing protein
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Protein Modeling Challenge
•
2014 Event Rules
www.stonybrook.edu/cesame
•
Pre-built model (40%)
•
On-site build (30%)
•
Written exam (30%)
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Ras Model 2013
•
•
•
•
Protein Databank File 5P21, Pai et al, model should show one chain of
residues 1-159
Model must arrive at Stony Brook by 4:30 p.m. February.
You can mail or hand deliver it. If mailed be sure to have tracking
information
Model and essays must be labeled with school and student names
Models are judge on:
• structural accuracy
•3-dimensional
topology
•Clarity
•Information content
•Include required
documents
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Written Exam 2013
•
Exam covers material in:
– Ras Resources listed in slides 8 and 9
– Information covered in the file “Learning Objectives for Ras”
– Jmol
– PDB file 5P21 and associated abstract
http://www.pdb.org/pdb/explore/explore.do?structureId=5p21
– Campbell, Biology, will be used a the material base for questions on
protein structure and function and cell communication.
– Taken as a group
– Available at the exam will be:
•
•
•
•
PDB file, abstract,
The structure summary page and sequence page for 5P21 from the Protein Data Bank
The molecule of the Month article
30% team score
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Ras GAP
•
•
•
On-site build
PDB file will be provided on the day of the exam
Students will build a portion of the receptor. They will be given: a
toober, selected amino acid side chains, a computer, jmol and the
pdb file.
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Protein Modeling Challenge With
National Science Content Standards
• Science and Technology
–
–
Abilities of Technological Design
Understandings about Science and Technology
• Life Science
– The Cell
– Physiology
• Science as Inquiry
–
Abilities Necessary to do Scientific Inquiry
• Physical Science
–
–
Structure and Properties of Matter
Chemical Reactions
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