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1Fall 2012
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.
Fall 2012
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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 sessionFall 2012
4Fall 2012
Joan Kiely, Stony Brook Universityjoan.kiely@stonybrook.edu
Debbie Pelio, Stony Brook Universitycesame@stonybrook.edu
http://www.stonybrook.edu/cesame
Linda Padwa, Stony Brook UniversityKristen La Magna, Stony Brook University
Shannon Colton, Ph.D., Technical AdvisorMilwaukee School of Engineering
http://cbm.msoe.edu/
5Fall 2012
• 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
Protein Modeling Challenge
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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.Fall 2012
7Fall 2012
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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• 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_Communication
Fall 2012
Protein Structure Resources
9Fall 2012
• Proteins are macromolecules• Amino acids are the basic building blocks of proteins• Working as a team, make an amino acid
Protein Structure
Nitrogen
Amino Group
Carboxyl Group
Alpha-Carbon
Sidechain (R-Group)
• is your amino acid L or D form?
10Fall 2012
D-Alanine 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
12Fall 2012
• A linear chain of amino acids is the protein “primary” structure
• A chain of amino acids will spontaneously form stable “secondary structures”, ie: beta-sheet or alpha-helix
• Hydrogen bonds may stabilize these structures
• Science researchers would like to understand what controls this folding.– http://fold.it/portal/
Proteins Have Secondary Structure
Alpha Helix
Beta-sheet
13Fall 2012
• Protein folding is due to the behavior of different chemical groups on amino acids in an aqueous environment
Proteins Fold Into a Tertiary Structure
Structural Biologists and Computer Scientists are collaborating improve our ability to predict protein structure and better understand MOTIFS and DOMAINS in proteinsYou 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/
14Fall 2012
• Proteins spontaneously fold into a specific three dimensional “tertiary” structure that governs a protein’s function
Proteins Fold Into a Tertiary Structure
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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 monthhttp://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/alphabetical_list.html
16Fall 2012
Molecule of the Month (MOM)
• A monthly PDB feature written by David Goodsellhttp://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/alphabetical_list.html
– Features a specific molecule
– Describes protein function
– Relates structure with functionThis 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
– 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.
• http://jmol.sourceforge.net/ has jmol for downloading and userguides.
• http://bioportal.weizmann.ac.il/oca-docs/fgij/index.htm– 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
18Fall 2012
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
20Fall 2012
Protein Modeling Challenge
• 2013 Event Rules www.stonybrook.edu/cesame
• Pre-build model (40%)
• On-site build (30%)
• Written exam (30%)
21Fall 2012
Estrogen Receptor Pre-Built Model 2012
• Protein Databank File 1A52 ESTROGEN RECEPTOR ALPHA LIGAND-BINDING 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 informationModels 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 abstract
http://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/cgi-bin/carddisp.pl?gene=ESR1Proteopedia has an unimpressive page http://www.proteopedia.org/wiki/index.php/Estrogen_receptorCellular Landscapes at Cell Signalinghttp://www.cellsignal.com/reference/landscapes/nucleus.html
Fall 2012
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Even More• See what scientist/artists can do with
information about Estrogen Receptors at String 9.0 http://string-db.org/newstring_cgi/show_input_page.pl?UserId=7yJna0cgDibk&sessionId=I6X6eyfULPNe admire the he image don’t try to learn the
Fall 2012