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Joined: 06/06/2013
Groups: Gargleblasters

You’ve finished the tutorials. What next? I think we should reward mastery of basic handfolding skills, and give points for progression at various levels of complexity. Things to consider would be the levels below. Fellow folders should pipe up or tell me where I’m off point.

Add more levels for new players where they can score points. The old timers can sit these out –or just be sure they earn no points. Players should pass out of a level when they have mastered each element. Awards for those who can master each level! I’m not sure how many skills should be in each level, but took a stab below. Correct me where I am wrong, missing something, or suggest which levels could be better defined.

Level 1 we teach people basic fold shapes like 2 and 3 plane proteins (two plane is surfing hot dogs or two sheet planes), a Koga ideal and a ferodoxin fold, a helix cluster. Showing someone how to see and fold a sheet plane at the core might be a useful “no belt” video to go with this. Lay out each step without assuming the watcher knows how to do anything. Show stubs to see how sheets line up. Gifted people will move through this quickly. We should also teach folders to look at backbone, clashing, voids and exposed parts of a fold to see how it can be improved. I’d start these puzzles with a given SS in a string, or even partly wonky with a few pieces to put into place. Perhaps some of both. There are plenty of existing folds to use as basis for these puzzles. Award for Level One is a Sheet Plane badge – sheet with wings. Earn award when get an acceptable fold for each basic shape just like tutorials have a minimum score.

Level 2 lets players learn how to spot foldable SS, so start with a non-mutatable string. Teach that sheets tend to alternate hydrophobes and hydrophiles, especially if not on the edge. We know that a glycine is likely to be part of a loop between SS elements, and that helices are two or three to one hydrophiles/phobes. We know certain patterns of proteins will likely be in a helix or sheet. Think of this as reverse blueprint, and use common loops like a GD or GN for sheet to sheet so folders learn to spot them. Basically these puzzles are smallish de novo folds of the shapes listed above. Can just lift some existing solutions to fold. Award for Level Two is a Surfing Hot Dog badge. Breed of dog to be selected by developers

Level 3 teaches some tricky bits. Barrels, a transmembrane protein (inside out barrel), cysteine bonds. QTTN if you plan to continue this format. These should complete the basic shapes. Need to learn that need at least 7 sheets for a barrel, cysteine bond is done from tip of side chain to tip of side chain and that angle must work for things to bond. Award with a barrel badge, or a keg :)

Level 4 is time to mutate. With basic shapes mastered, can teach players to build a shape and mutate to fit. At this point, the monomer puzzles will be within reach. Work through varying types of filters – must be no more than 50% helix, can be all helix, ideal loops, etc. Must have a core. Award extra points for pi sandwiches(aromatics lined up in the core). Teach how to check with RAMA map or Blueprint. Stick to small monomers of a fixed size for this. Also, teach H bonding to improve fold stability and points. Badge is Ice Cream sandwich filled with pi.

Level 5 plus should be open to all. Time to learn how to dock a ligand, mutate and/or change the SS around a ligand, work ED, work contact maps, work symmetry. Many of us long timers still can’t do all these things, so this might be what is currently “intermediate” and open to all. Congratulate on moving to intermediate with a fun and geeky badge. Or perhaps a badge for each type of puzzle and throw out the long time folders who can do some of these things in their sleep (anyone in top 50 or so). Require a minimum number of points as mastery of each puzzle type. Make the puzzles workable as a teaching tool. So make sure the contact map has some neat diagonal sections that are obviously helix and is mostly complete, put some long aromatic side chain sections into the ED so players can spot them. Better folders can use these to hone skills, but not earn points.

Current revisits should be intermediate. Time for the messy world of real proteins. Similarly, monomer, H bond and symmetry puzzles can fit this label, though perhaps it needs a new name. Not sure if contact maps go here or next level up. I think it depends on the person. Novice points might also be appropriate for players below the top 50.

Alphatoxin, other large “challenge” puzzles, ED need to be classified advanced. I think fewer than 20 players can really work the ED puzzles so this is just good labelling. I would not lock this or the prior level out to any player – rather use the labels as truth in advertising. Sort of like Angry Birds – ED is a hard level to pass while the other levels are easier. I’d also put any large protein into the advanced class as some people are working these puzzles on antique equipment (myself amongst them).

Please offer suggestions. Recommendations from new players in particular would be helpful. How do we keep this fun for everyone? Sometimes our new players jolt us out of a rut and bring fresh and useful insight into the game for all of us, so you are far more important than you realize.

Happy folding


Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, RosettaCommons