Astellas Protein Modeling
Challenge
February 28, 2013
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SIZE RESTRICTION NEW THIS YEAR
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.
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Location
• Registration in SAC Ballroom A
• Testing and Model Building on the 3rd floor of
the SAC
• The Astellas Scientists want to CHAT with
your students so after the exam and modeling
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
joan.kiely@stonybrook.edu
Debbie Pelio, Stony Brook University
cesame@stonybrook.edu
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:
– Meet and get to know the estrogen
receptor and why it is an important target
for rational drug design
– Build models that illustrate what you know
about the receptor, steroid hormone
signaling, and breast cancer.
– 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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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 Molecule of the
Month, THE ESTROGEN RECEPTOR,
•
The category Infrastructure and Communication,
subcatagory communication with hormones has
useful background
articles.http://www.pdb.org/pdb/101/structural
_view_of_biology.do?c=Infrastructure_and_Com
munication
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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 (it is not the estrogen
receptor)
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
•
2013 Event Rules
www.stonybrook.edu/cesame
•
Pre-build model (40%)
•
On-site build (30%)
•
Written exam (30%)
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Estrogen Receptor
Pre-Built Model 2012
•
•
•
Protein Databank File 1A52 ESTROGEN RECEPTOR ALPHA LIGANDBINDING DOMAIN COMPLEXED TO ESTRADIOL
Model should be based on residues 345-504 of chain A
Model must arrive at Stony Brook by 4:30 p.m. February 21. You can
mail or hand deliver it. If mailed be sure to have tracking information
Models are judge on:
• structural accuracy
•3-dimensional
topology
•Clarity
•Information
•Include required
documents
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Written Exam 2013
•
Exam covers material in:
– The Dynamic Structure of the Estrogen Receptor
– Power Point Presentation from Bio364
– Information taken from the following government sites:
• http://www.cancer.gov/cancertopics/types/breast
• http://www.uspreventiveservicestaskforce.org/index.html
• http://www.cancer.gov/cancertopics/understandingcancer
– Jmol
– PDB file 1A52 and associated
abstracthttp://www.pdb.org/pdb/explore/explore.do?structureId=1a52
– 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 1A52 from the Protein Data Bank
The molecule of the Month article
30% team score
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Estrogen Receptor
•
•
•
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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Want More?
Bioinformatics sites for ESR alpha:
http://www.genecards.org/cgibin/carddisp.pl?gene=ESR1
Proteopedia has an unimpressive
page
http://www.proteopedia.org/wiki/ind
ex.php/Estrogen_receptor
Cellular Landscapes at Cell Signaling
http://www.cellsignal.com/reference
/landscapes/nucleus.html
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Even More
• See what scientist/artists can do with
information about Estrogen Receptors
at String 9.0 http://stringdb.org/newstring_cgi/show_input_page.
pl?UserId=7yJna0cgDibk&sessionId=I6
X6eyfULPNe
admire the he image don’t try to learn the
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