Protein Modeling Challenge Science Olympiad Trial Event Shannon Colton, Ph.D., Event Supervisor Gary Graper, Event Technical Advisor

Protein Modeling Challenge To compete successfully in the Protein Modeling Challenge, you will: – Identify basic features of protein structure – Explore protein structure with the computer visualization program Jmol – Create physical models using the flexible modeling media, Mini-Toobers 2

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! 3

Protein Structure Proteins are macromolecules Amino acids are the basic building blocks of proteins 4 Nitrogen Amino Group Carboxyl Group Alpha-Carbon Sidechain (R-Group)

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 (www; this link will bring you to a webpage that has multiple pdfs pertaining to protein structure at the bottom of the page)www – Collection of models and activities: Introduction To Protein Structure (ITOPS) (www)www – MSOE Model Lending Library (www)www) 5

Amino Acids Have Unique Chemical Characteristics Each amino acid has the same “backbone” structure, but has different chemical groups (R groups or sidechains) attached Construct an amino acid and a dipeptide with a molymod kit (ITOPS) (pdf)pdf 6 NH 2 -CH-COOH R

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: beta-sheet or alpha- helix Construct an alpha-helix and beta- sheet activity (ITOPS, Introduction To Protein Structure) (pdf)pdf 7 Alpha Helix Beta-sheet

Proteins Fold Into a Tertiary Structure Proteins spontaneously fold into a specific three dimensional “tertiary” structure that governs a protein’s function 8

Proteins Fold Into a Tertiary Structure Protein folding is due to the behavior of different chemical groups on amino acids in an aqueous environment Explore amino acid sidechain chemistry and protein folding with the Amino Acid Starter Kit Activity (ITOPS, Introduction To Protein Structure) (pdf)pdf 9

Defining Protein Structure The 3-dimensional structure of proteins is often determined by x-ray diffraction or NMR analysis Each atom in a protein is assigned a specific set of X, Y, Z coordinates in 3D space to create a PDB data file 10

Protein Data Bank PDB file lists the X, Y, Z coordinates for each atom in a protein Protein Data Bank website is the location to download PDB files (www)www PDB Molecule of the Month features the structure and function of a different protein each month (www)www 11

Molecule of the Month (MOM) A monthly PDB feature written by David Goodsell – Features a specific molecule – Describes protein function – Relates structure with function 12 Ribonucleases September 2008 Molecule of the Month (www)www

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 We will use this website on the day of competitions.website 13

RasMol versus Jmol Many of you may be familiar with RasMol. RasMol is a great program and may be continued to be used by Science Olympiad Teams. However, since there have not been updates to RasMol to allow for it to operate easily on Macs, Jmol will be the computer visualization program to be used in the future. The commands that you have used in RasMol are almost the same in Jmol. You may practice using Jmol by using the this website.website 14

Exploring Protein Structure with Jmol Jmol allows you to identify elements of protein structure – Helix (magenta) – Sheet (yellow) – N-terminus (or first amino acid in the protein (blue) – C-terminus (or the last amino acid in the protein) (red) – Amino acid sidechains (CPK) – Alpha-carbon backbone model format 15

Jmol Resources Use the following resources as tools in learning Jmol: – Jmol free download (www)www – Alternatively, use the same website that will be used on the day of the competition (www)www – Assistance on downloading and installing Jmol on your computer (pdf)pdf – Reference Card of Jmol commands, condensed (www)www) 16

Jmol Exercises Explore the structure of a zinc finger domain and beta-globin proteins and practice RasMol – Zinc Finger Exercise (www) Answers (www)www – Beta Globin Exercise (www) Answers (www)www 17

Mini-Toober Models Mini-Toobers are a flexible modeling media Developed by 3D Molecular Designs (3DMD) with a Small Business Initiative Research grant (SBIR) from the National Science Foundation (NSF) (www)www 18

Create Physical Mini-Toober Models Identify protein structural features using Jmol (ie: helix, sheet) Identify important amino acid sidechains that play a significant role in the function of the protein – This can be accomplished by exploring the story of the protein – David Goodsell’s Molecule of the Month is a great place to start 19

Mini-Toober Models (cont.) Mark location of structures on Mini-Toober using a marker or pen Fold Mini-Toober into a 3D model representing protein based on the image you created using Jmol 20

Example Protein: Zinc Finger Protein Zinc finger proteins bind DNA A zinc finger domain contains a short alpha-helix, 2 beta-strands and conserved Cys, His amino acids that bind a molecule of zinc For more information about the zinc finger protein, you can read David Goodsell’s Molecule of the Month (www)www) 21

Zinc Finger Folding Exercise Zinc Finger Folding Activity is available from MSOE Lending Library – This activity will allow you to fold a toober into a zinc finger to practice modeling proteins (www)www Challenge: Download the 1ZAA pdb file, create an image in Jmol, identify key structural features, and fold a Mini-Toober model 22

Protein Modeling Challenge Science Olympiad Trial Event 2009 Event Rules (www)www Protein Modeling Event – Pre-build model (40% of total score) – On-site build (30% of total score) – Written exam (30% of total score) 23

Protein Modeling 2008 Prebuild The 2008 Protein Modeling Event focused on the calcium-binding protein – Calmodulin, described in the August 2003 Molecule of the Month (www)www Teams constructed a model of the entire calmodulin protein for the prebuild Prebuild Rubric (pdf) – 40% of the final scorepdf 24

Protein Modeling 2008 Onsite Builds For onsite competitions, selected regions of the calmodulin were modeled Regional Onsite Build Rubric (pdf) – 30% of the regional final scorepdf State Onsite Build Rubric (pdf) – 30% of the state final scorepdf 25

Protein Modeling 2008 Exam Teams also completed an exam based on protein structure and specifically on the function of calmodulin 2008 State Exam (pdf) – 40% of final scorepdf) 26

National Science Content Standards Science and Technology – Abilities of Technological Design – Understandings about Science and Technology Life Science – The Cell Science as Inquiry – Abilities Necessary to do Scientific Inquiry Physical Science – Structure and Properties of Matter – Chemical Reactions Detailed Alignment (www)www 27

PDB Newsletter Features Protein Modeling PDB Newsletter, No. 26, Summer 2005 (www)www PDB Newsletter, No. 33, Spring 2006 (www)www PDB Newsletter, No. 36, Winter 2008 (www)www PDB Newsletter, No. 38, Summer 2008 (www)www 28

Protein Modeling Supports Science Olympiad Mission Emphasis on teamwork 29

Protein Modeling Supports Science Olympiad Mission Provides curriculum training workshops and web based distribution of materials from the MSOE Center for BioMolecular Modeling web site (www)www 30

Protein Modeling Supports Science Olympiad Mission Brings science to life, shows how science works, emphasizes problem solving aspects and understanding of concepts 31

Protein Modeling Supports Science Olympiad Mission Promotes partnerships among community, businesses, industry, and education 32

Protein Modeling Supports Science Olympiad Mission Promotes high level of achievement and demonstrates students can perform at levels approaching practicing scientists 33

CBM Programs Teacher Professional Development (www)www – Genes, Schemes, Molecular Machines – Modeling the Molecular World – Molecular Stories of Research-Based Health Care SMART Teams (Students Modeling A Research Topic) (www)www MSOE Model Lending Library (www)www Science Olympiad Protein Modeling Challenge (www)www 34

Additional Information For more information, or to ask questions, please contact: Shannon Colton, Ph.D., or 35