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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 sessionFall 2012

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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/

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• 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

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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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• 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

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Protein Structure Resources

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• 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?

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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

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• 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

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• 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/

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• 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

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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

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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 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

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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

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