The 2018-19 Theme:

Anti-CRISPR: The Arms Race Continues

Be extra sure to explore the information in all three tabs below


CRISPR and Anti-CRISPR Protein & DNA Structure The 2018-19 Proteins

Welcome!
To the 2018-2019 Science Olympiad Protein Modeling Event Webspace

This year’s event focuses on CRISPR and anti-CRISPR Proteins. Explore the introduction video and additional content below to prepare for this year's event.





Get Your Head Around CRISPR

CRISPR technology has already revolutionized the molecular biosciences. Many excellent videos have appeared that explain how this technology works. Here are a few of our favorites – directed toward a variety of audiences and presented at varying levels of detail.



What Is CRISPR?

Bozeman Science / Paul Andersen provides a very nice overview of the CRISPR System.





CRISPR Gene Editing and Beyond

A protein-centric video of CRISPR, from Nature (a weekly science journal).





CRISPR: History of Discovery

A Singapore NIE video that documents the historical milestones in the discovery of the CRISPR system.





What is the PAM?

An IGI Whiteboard Lesson from the Doudna lab.





CRISPR and the Future of Human Evolution

PBS Digital Studios and the It’s OK To Be Smart series. . . Just for fun. . .





An Interview with Sam Sternberg

And for you over-achievers who are really hooked on CRISPR, check out this hour-long interview/podcast with Sam Sternberg --Jennifer Doudna’s co-author of the book entitled A Crack in Creation. Once you have watched the videos suggested above, you may find that this podcast will answer many of the questions you had as you thought more deeply about how the CRISPR system works.

http://hwcdn.libsyn.com/p/9/8/f/98f37d51cbb8ea2b/TWiM184.mp3?c_id=23139702&cs_id=23139702&expiration=1539629661&hwt=ef0772f1a06d1692d9ba6342ac10db9a

Structure Papers for AcrII4A – an anti-CRISPR Protein

Researchers have only recently began discovering and characterizing viral proteins that can bind to and inhibit the action of CRISPR Cas9. AcrII4A, the focus of your pre-build model, is one such anti-CRISPR protein. The molecular structure of the AcrII4A protein was determined in 2017, almost simultaneously by two different labs. The papers (i.e., the primary citations) describing these structures are provided below.


Inhibition Mechanism of an Anti-CRISPR Suppressor AcrIIA4 Targeting SpyCas9
Hui Yang and Dinshaw J. Patel, Molecular Cell 67, 117–127, 2017 http://dx.doi.org/10.1016/j.molcel.2017.05.024



Structural basis of CRISPR–SpyCas9 inhibition by an anti-CRISPR protein
De Dong, Minghui Guo, Sihan Wang, Yuwei Zhu, Shuo Wang, Zhi Xiong, Jianzheng Yang, Zengliang Xu & Zhiwei Huang, Nature, 546, 436-439 (2017)


Ask the CBM!




Answered Questions:

Additional answers will be added as more questions are submitted and audio recordings are completed.



1. When is the pre-build visualization environment going to be updates for this season?

2. How does the PAM know what the DNA sequence is?

3. What are we supposed to model for the pre-build?

4. Why are there 2 papers. Are we supposed to read both of them?

5. A lot of the sidechains on AcrllA4 interact with the other complexes as mentioned in the papers. How would we model that on the AcrllA4 protein without having the other complexes built?

6. In the technical papers on the mechanism of action of the anti-CRISPR ACrIIA, what do the yellow and red highlighted areas mean?

7. How do scientists get CRISPR to affect all the cells of a body?

8. Why do two unconnected regions of protein show up when the amino acid residue range is selected?

9. What is the difference between the various Cas proteins (ie: Cas1, Cas2, Cas9, etc.)?

10. What is the sgRNA?

11. What is the purpose of the tracer RNA when the crRNA is the part that actually binds to the viral DNA?

12. In Jsmol, how do I know I have the correct chain?

13. Should we download the Jsmol program or only use the online prebuild environment?

14. For our prebuild model, should we worry about the exact number of amino acids per helix?

15. What should we do if the restrict command in Jmol is not working?

16. Is there an undo or a redo button in the online environment?

17. My mini toober is about 127cm long, is that wrong?

18. In humans, where does the cut section go when the DNA is replicated?

Click to Open the Second Tab: Protein & DNA Structure

In order to truly appreciate and successfully model this year's Protein Modeling Event structures, a thorough understanding of protein structure is needed. This section will explore these amazing macromolecules in more detail using suggested physical model kits, online resources and additional websites.

Protein Structure

Proteins are long linear sequences of amino acids
that fold into complex 3-dimensional shapes
following basic principles of chemsitry.

In this first of two videos on protein folding, Tim Herman, Ph.D. from the MSOE Center for BioMolecular Modeling uses the Water Cup from 3D Molecular Designs to demonstrate some basic principles of chemistry.




In this second of two videos on protein folding, Tim Herman, Ph.D. from the MSOE Center for BioMolecular Modeling uses the Amino Acid Starter Kit from 3D Molecular Designs to demonstrate how the basic principles of chemistry directly affect protein folding.




In this video, Tim Herman, Ph.D. from the MSOE Center for BioMolecular Modeling uses the Alpha-helix Beta-sheet Construction Kit from 3D Molecular Designs to demonstrate the form and function of secondary structures in proteins.






Protein Databank (www.rcsb.org) Resources

Learn about protein structure and function with this overview printout and video developed by the RCSB Protein Databank.

Protein Structure Jmol Tutorials

The Protein Structure Jmol Tutorials walk through the four levels of protein structure using interactive Jmol molecular visualizations, including real protein examples with interactive controls.

3D Molecular Designs Educational Kits

These engaging, hands-on kits make learning protein structure basics easy. Users will fold a protein while exploring how the chemical properties of amino acids determine its final structure.

DNA Structure

DNA carries your genetic information in that it determines the sequence of amino acids in your proteins. These protein sequences, in turn, determine the shape and structure of your proteins. Proteins then work like nano-scale molecular machines, carrying out countless different tasks in your body.

The human genome is divided into 23 chromosomes pairs, found in the nucleus of every cell. To keep these long linear polymers of DNA from getting all tangled up, the DNA of each chromosome is packaged into repeating structural units called nucleosomes. The DNA exists as a double–stranded structure with two twisting backbones running in opposite directions and four different bases: adenosine (A), thymine (T), guanine (G), and cytosine (C).

The visual representation of DNA above is completely interactive and can be rotated in 3-dimensions by clicking and dragging with your mouse.

The four types of bases that make up DNA can form base-pairs between the two strands of double-stranded DNA. Adenosine only pairs with thymine and guanine only pairs with cytosine, making the two strands of DNA complimentary. The sequence of bases is often represented with abbreviated letters as shown below. It is this order of DNA bases that contains the key information needed for creating proteins and passing along genetic information.

For more information on DNA structure, explore the RCSB PDB's Molecule of the Month feature on DNA article by the molecular illustrator, David Goodsell.


Click to Open the Final Tab: This Year's Proteins


★ RULES Clarification! ★

The official Rules for the Protein Modeling event are incorrect. As clarified at https://www.soinc.org/events/rules-clarifications, the rules should read:

1. DESCRIPTION, (edits in bold): Students will use the computer visualization and online resources to construct physical models of the CRISPR Cas9 protein and Anti-CRISPR protein that are being engineered to edit plant and animal cell genomes, and answer a series of questions about the chemistry of protein folding and the interaction of structure and function for model proteins.

THE COMPETITION Part I: The Pre-Built Model, a. (edits in bold): Participants will use the program Jmol/JSmol to visualize a model of residues 1-85 of the Anti-CRISPR protein, AcrII4A, based on the coordinate data found in the 5vw1.pdb file. The 5vw1.pdb file can be accessed for free from the RCSB Protein Databank (www.rcsb.org). Jmol/JSmol can be accessed at http://cbm.msoe.edu/scienceOlympiad/designEnvironment/prebuild.html for free.



Current Rules

If you’ve participated in the Science Olympiad Protein Modeling Event in previous years, please note that there were a few changes to the rules in the 2018-2019 season. Refer to the official rules for explicit details, but the changes include:

  1. size limitations for pre-build models
  2. size and format of card detailing creative additions to the pre-build model
  3. requirement that models be sturdy enough that judges can pick up and rotate models for judging
  4. Each team may bring one 8.5” x 11” sheet of paper that may contain information on both sides in any form and from any source.


Here is a sample notecard describing creative additions (modeling beta globin):



The table below lists the proteins that will be featured as the 2018-19 pre-build as well as the various on-site builds at invitational, regional, and state competitions.

Be Sure to Click on Each Protein Listed Below to reveal additional resources that you should explore as you prepare for each level of competition. In addition to providing the pdb file for the protein that will be featured, these links also provide a copy of the original research paper (the "primary citation") that reported the protein's structure. Questions regarding the paper and the structure presented in the PDB file will be asked on the exam you will complete at each competition.

Pre-Build Model AcrII4A Anti-CRISPR Protein 5vw1.pdb
X

Coordinates for the Model

The 2018-19 Pre-Build Model should represent amino acids 1-85 of chain B of the PDB file 5vw1.pdb.

You can access the Pre-Build online design environment at http://cbm.msoe.edu/scienceOlympiad/designEnvironment/prebuild.html. Also study what types of additional features could be highlighted in the pre-build model in Section 3.

Background Information

Researchers have only recently began discovering and characterizing viral proteins that can bind to and inhibit the action of CRISPR Cas9. AcrII4A, the focus of your pre-build model, is one such anti-CRISPR protein. The molecular structure of the AcrII4A protein was determined in 2017, almost simultaneously by two different labs. The papers (i.e., the primary citations) describing these structures are provided below.

Inhibition Mechanism of an Anti-CRISPR Suppressor AcrIIA4 Targeting SpyCas9
Hui Yang and Dinshaw J. Patel, Molecular Cell 67, 117–127, 2017 http://dx.doi.org/10.1016/j.molcel.2017.05.024

Structural basis of CRISPR–SpyCas9 inhibition by an anti-CRISPR protein
De Dong, Minghui Guo, Sihan Wang, Yuwei Zhu, Shuo Wang, Zhi Xiong, Jianzheng Yang, Zengliang Xu & Zhiwei Huang, Nature, 546, 436-439 (2017)

Invitational On-site Model CRISPR-Cas9 5f9r.pdb
X

Coordinates for the Model

The 2018-19 Invitational On-Site Model will be taken from CRISPR-Cas9 based on the PDB file 5f9r.pdb.

Background Information

Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein.

Regional On-site Model CRISPR-Cas9 5f9r.pdb
X

Coordinates for the Model

The 2018-19 Regional On-Site Model will be taken from CRISPR-Cas9 based on the PDB file 5f9r.pdb.

Background Information

Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein.

State On-site Model CRISPR-Cas9 5f9r.pdb
X

Coordinates for the Model

The 2018-19 State On-Site Model will be taken from CRISPR-Cas9 based on the PDB file 5f9r.pdb.

Background Information

Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein.

National On-site Model CRISPR-Cas9 5f9r.pdb
X

Coordinates for the Model

The 2018-19 National On-Site Model will be taken from CRISPR-Cas9 based on the PDB file 5f9r.pdb.

Background Information

Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein.



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★ Please Note: The was an incorrect version of the 2017-2018 season rules for the Protein Modeling Event posted to the Science Olympiad home website (https://www.soinc.org/). Please check your copy of the rules to make sure you are using the 11/13/17 revised version. (Influenza is this year's topic.)