1. Fall 20121 Astellas Protein Modeling Challenge February 28, 2013

2. 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 20122

3. Location Registration in SAC Ballroom A Testing and Model Building on the 3 rd 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 Fall 20123

4. 4 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/ http://cbm.msoe.edu/

5. Fall 20125 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

6. Useful Web sites Protein Data Bank http://www.pdb.org/pdb/home/home.do http://www.pdb.org/pdb/home/home.do Center for Biomolecular Modeling http://cbm.msoe.edu/ 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. http://cbm.msoe.edu/stupro/smart/resources.html Fall 20126

7. 7 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!

8. 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 linkshttp://cbm.msoe.edu/teachRes/index.html 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 municationhttp://www.pdb.org/pdb/101/structural _view_of_biology.do?c=Infrastructure_and_Com munication Fall 20128 Protein Structure Resources

9. Fall 20129 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?

10. Fall 201210 D-Alanine L-Alanine

11. Fall 201211 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 NH 2 -CH-COOH R

12. Fall 201212 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

13. Fall 201213 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 proteins You can explore amino acid sidechain chemistry and protein structure through the game and programs at: Fold It: http://fold.it/portal/http://fold.it/portal/ or Rosetta@Home http://boinc.bakerlab.org/ http://boinc.bakerlab.org/

14. Fall 201214 Proteins spontaneously fold into a specific three dimensional “tertiary” structure that governs a protein’s function Proteins Fold Into a Tertiary Structure

15. Fall 201215 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.dohttp://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

16. Fall 201216 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.

17. Fall 201217 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://jmol.sourceforge.net/ 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

18. Fall 201218 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

19. Fall 201219 Mini-Toober Models (cont.) Mark location of structures on Mini-Toober Fold Mini-Toober into a 3D model representing protein

20. Fall 201220 Protein Modeling Challenge 2013 Event Rules www.stonybrook.edu/cesame Pre-build model (40%) On-site build (30%) Written exam (30%)

21. Fall 201221 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 information Models are judge on: structural accuracy 3-dimensional topology Clarity Information Include required documents

22. Fall 201222 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=1a52http://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

23. Fall 201223 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.

24. Fall 201224 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

25. Want More? Bioinformatics sites for ESR alpha: http://www.genecards.org/cgi- bin/carddisp.pl?gene=ESR1 Proteopedia has an unimpressive page http://www.proteopedia.org/wiki/ind ex.php/Estrogen_receptor http://www.proteopedia.org/wiki/ind ex.php/Estrogen_receptor Cellular Landscapes at Cell Signaling http://www.cellsignal.com/reference /landscapes/nucleus.html Fall 201225

26. 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=I6 X6eyfULPNe admire the he image don’t try to learn thehttp://string- db.org/newstring_cgi/show_input_page. pl?UserId=7yJna0cgDibk&sessionId=I6 X6eyfULPNe Fall 201226