Saturday, August 10, 2013

Protein Folding can be fun in more ways than one

Although this blog often features serious discussions of scientific research, I am myself a big fan of board and card games. In fact, I am an avid chess player, dedicated enough to play in (and sometimes place) in tournaments in the New York area. I even run another blog devoted to Chess and the ways in which it intersects with Science.

One feature of gameplay that attracts me is how it can be adapted for educational uses. In indirect and abstract ways Chess has taught me a multitude of lessons. Other games, such as Scrabble and Boggle (and some iPhone adaptions or derivatives) may help to improve one's vocabulary, even if just slightly. More to the point, however, I recently began to think of ways to devise some games that will make certain concepts in Microbiology and Molecular Biology easier to grasp and fun to learn.

Here I am showcasing the first of these efforts: a game about protein folding. Protein folding describes the manner in which a protein, which is a polymer (or string) of amino acids in a particular sequence, folds into a 3-dimensional shape. For a refresher on the relationship between our genetic material and a protein's shape, please refer to my crash course on the central dogma of molecular biology. The 3D configuration of a protein is extremely important in microbiology and molecular biology. A majority of the behaviors a microbe carries out are executed by proteins, and protein structure usually dictates function.

Before giving you a description of my invention, which is meant solely for edutainment, I need to point out another game that revolves around protein folding. FoldIt, designed by David Baker's laboratory group, is at once an entertaining computer game and a brilliant idea. Since it is difficult for computers to accurately determine the structure of a protein from the amino acid sequence alone, Baker uses FoldIt to enlist the help of people all across the world in this task. By taking protein structures and turning them into puzzles, FoldIt has players tweak the shapes of proteins and rewards them with points for more stable structures. Apart from actually being quite fun (especially if you are a fan of puzzle games), playing this game actually advances scientific research and protein structure prediction.

My game, which I tentatively call "Protein Power" (for lack of a better name), is different. It is a board game designed simply for fun and to teach some concepts behind protein folding. It resembles in some ways both Scrabble and primitive protein folding models (ones in which polar and hydrophobic beads were placed upon a grid). The screen shot above gives you a glimpse into the game: you place amino acid tiles upon a board and score points for connections or interactions between them: hydrophobic interactions are rewarded, salt bridges score points as well. Hopefully, through the game players will become familiar with the idea that protein folding involves hiding hydrophobic residues from water and forming energetically stable structures. At the very least, I hope they have fun playing and that the gameplay is not too derivative (I think it's actually fairly original). Unlike Foldit, it is a multiplayer, strategic board game.

Select 'Read More' to see the rules for the game and example gameplay.

Below is a description of the materials of the game as well as the rules, and a short example (1 turn by each of two players). This game is a simply a prototype, and I encourage educators to adapt it as they see fit. I am currently exploring ways I can make a mass-produced, physical version of the game as well as electronic versions for both computers and smart phones. Drop me a line if you'd like to help!

Game Materials (Dimensions and tile counts can be changed)

1. The Board

Double Grid (Squares and Circles), unadorned otherwise

2. The Amino Acid Pieces:

25 Yellow (Hydrophobic)
20 Green (Polar)
20 White (Neutral) with 10 of the White having Kinks (not all four directionals)
10 Red (Negative)
10 Blue (Positive)
10 Purple (Aromatic)
8 Orange (Cysteine)
6 Blue Starts (NH2+)
6 Red Ends (COOH)

3.Special Tiles

20 Light Blue Water Drops (H20)
6 Light Blue Ions (Mg2++, Zn2++, etc)

4. The Interactions

4 Orange-Orange (Sulfur Bond)
10 Red-Blue (Salt Bridge)
50 Yellow-Yellow (Hydrophobic Interaction)
10 Purple-Purple (Aromatic Ring Stacking)
20 Green-Green (Polar / Hydrogen Bond)
20 Green-Water (Polar / Hydrogen Bond)
20 Green-Red (Polar / Hydrogen Bond)
20 Green-Blue (Polar / Hydrogen Bond)
20 Water-Blue (Polar / Hydrogen Bond)
20 Water-Red (Polar / Hydrogen Bond)

Game Rules

The Scoring System:

9 Points for Orange-Orange (Sulfur Bond)
7 Points for Red-Blue (Salt Bridge)
5 Points for Yellow-Yellow (Hydrophobic Interaction)
3 Points for Purple-Purple (Aromatic Ring Stacking)
1 Points for Green-Green (Polar / Hydrogen Bond)
1 Points for Green-Water (Polar / Hydrogen Bond)
1 Points for Green-Red (Polar / Hydrogen Bond)
1 Points for Green-Blue (Polar / Hydrogen Bond)
1 Points for Water-Blue (Polar / Hydrogen Bond)
1 Points for Water-Red (Polar / Hydrogen Bond)
2 Points for placing a 'N' (N-terminal tile)
2 Points for placing a 'C' (C-terminal tile)


1. Players take turns choosing tiles from a random pile. The first player to choose a 'N' tile (N-terminus) will keep that tile will begin play. This player keeps this 'N' tile, all others are scrambled again.

2. After the order of play is established (either clockwise or counterclockwise from the first player), each player chooses 7 tiles at random (except for the first player, who only chooses six).

3. On each turn, players place down tiles in the square boxes, following the directionals. Only the 'N', Water, and Ion tiles may be placed anywhere on the board (excluding special rules).

4. After placing their tiles, players may score by placing appropriate 'connection / interaction' dots in between the tiles they placed.

5. After each turn, a player will take tiles at random until they once again have 7 tiles.

Special Rules:

1. Amino Acid Tiles must be placed in N to C direction, along arrows and lines

2. Special Tiles (Water and Ions) can be placed anywhere, except when violating other rules

3. Yellow Tiles and Water Tiles cannot be placed next to each other

4. Yellow Tiles cannot be placed next to Red or Blue Tiles unless these are paired

5. Any single red or blue tile can only form one salt bridge. Likewise, single orange tiles can only form one sulfur bond.

6. At the end of a particular chain, a player may only place another amino acid or a C-terminal tile. Water, Ions, or N-terminal tiles cannot be placed in a manner that blocks a directional.

7. Tiles may not be placed in a manner that has the arrow pointing off of the grid.

8. No tiles may be placed after a C-terminal tile; a new chain must be started in order to continue.

Winning the Game:

Various conditions for winning may be used. As in Scrabble, play could continue until tiles are exhausted.

Alternatively, I recommend play end and a winner declared on one or more of the following criteria:

1. First player to reach 100 points

2. Highest scoring player wins in the event that a C-terminus is placed down and there are no other N-terminal tiles available (or already in a player's stock of tiles)

3. Highest scoring player wins in the event that a player has no remaining legal moves (for example, a player only has Yellow tiles but their only available place to play them would be adjacent to a water tile, which is illegal.)

Example Game:

Starting position is shown below. Only a quarter of the board is shown for illustrative purposes (The upper left corner: actually game board should be 4x larger)

Click on the image for a larger version

Each player has 7 tiles; one player possesses the N-terminal tile, and thus can go first, placing it anywhere on the board. This can be followed with some or all of his remaining tiles.

The first player has taken his turn and placed all 7 of his tiles. You can notice that they follow the direction of the arrow, starting from the N-terminus. They run N-Orange-Yellow-Gray-Purple-Yellow-Green. Next, the player can score points by placing dots between 'connections' or 'interactions'.

As you can see, the Yellow-Yellow interaction (Hydrophobic interaction) is worth 5 points. Adding to that the 2 point bonus for going first (The N-terminal tile), this gives Player 1 a score of 7 points for the round. Next, it is the second player's turn.

As you can see, the second player has continued the chain by adding an Orange-Green-Red-Gray sequence, starting from where the first player left off. He/she has also placed both water tiles on the board. and was left with a single Yellow (Hydrophobic) tile unplayed. Next, it is time to assign the score for this turn.

As you can see, the second player gets points for 3 different polar interactions (two red-green, one green-water) and a salt bridge (red-blue). This is a total of 10 points. The second player is thus currently in the lead with a score of 10 to 7.

It is worth noticing the placement of the water tiles. One of them was placed next to a polar residue, to create hydrogen bonds and score points. Another was placed seemingly in the middle of nowhere. This was a strategic move, which prevents the placement of yellow tiles nearby, where they could (and would) have scored points. Of course, such a strategy makes more sense when you are ahead on the scoreboard (limiting scoring possibilities).

In addition to being a fun strategy game, it may be possible to form 'find the best move' puzzles. Stay tuned for this and more.

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