The Basic FoldIt Controls and the Way Nature Folds Protiens

When playing FoldIt you have some controls you use all the time and some you use less frequently.  The Actions you use all the time are Shake Side chains, Wiggle  All, Wiggle Backbone, Wiggle Side chains, Unfreeze Protein, Remove Bands, Disable Bands, and (unshown) Enable Bands.  In addition to these Actions, I have demonstrated a frozen segment and a band between a segment and space.  You can also band and freeze side chains.  I have also brought up the local action popup menu where you can Freeze or Tweak the structure(if the segment is part of a helix or sheet) or Rebuild, Shake, or Wiggle the protein as bounded by frozen segments.  The Behavior menu item brings up a slider for Clashing Importance.  Some puzzles let you Mutate Side chains.  Some puzzles have ghost guides of the native protein fold.  Some puzzles allow the protein to be threaded by aligning it against other proteins with known folds.  The Modes are Pull, Structure, Note, and Design.  I play most of the game in Pull mode.  Structure mode lets you indicate a segment as being part of a loop, helix, or sheet.  Note mode lets you add comments to segments so you can document what you want to do and where.  When a Puzzle lets you mutate the protein Design mode lets you change the amino acid at a particular segment and to insert or delete segments in puzzles that let you change the number of segments.

Since the idea of the game is to help science these control need to be analogs of natural processes.  When you Google Protein Shape you find some interesting articles about why protein take the shapes they do.   When I ran the query the first page returned was to The Rules of Protein Structure by J Kimble, the second was to The importance of protein folding by Joachim Pietzch.  Later I found How Proteins Get In Shape, an unattributed article on the Pittsburgh Supercomputing Center Website.  A scan of the cited articles and others you find from the search should give you an idea about the shake and wiggle actions and even the clashing importance.  The freeze and band controls are a bit more mysterious.  For the most part the take on the role of all the natural processes too complex to individually model with today's technology.

You can help science by more than just playing the game.  You can record the techniques you use in "Recipes" and share them with others.  In a previous article I touched on recipes.  I will return to them in my next article.

Why Humans Fold Proteins.

OK, I guess I need to step back for a moment. 

Some wonder how we are helping science by playing a game.  It seems like we aren't doing anything a computer can't do faster.  Nature doesn't need us to fold proteins.  Empirical science looks at nature to inform theory.  Just how are we helping?

This is the solution the first introductory puzzle.  All one has to do is move one of the side chains away from the other.   Once one gets past this first introductory puzzle the Actions menu has a button, "Shake Side chains", that will do it automatically.  It's a simple move.  Just how are we helping?

As it turns out, even simple proteins are quite complex.  Proteins are composed of a chain of amino acid residues.  There are twenty two standard amino acids and many non-standard amino acids.  Living cells use the process protein synthesis to build the various proteins of life encoded in DNA.  Science hasn't learn how to predict the way any particular protein will fold and the process is computationally complex.

When humans play FoldIt  they are using idealized versions of natural processes to fold models of proteins.  The game scores the folded protein based upon the energy left in it where the lower the energy the higher the score.  Intermediate positions are recorded and the sponsors of the game can use this to improve their model of how proteins fold.  We are solving a problem in what appears to be less steps that mathematics predicts it should take.  Being able to replicate that process even if it isn't understood will make designing proteins to fight diseases a reality.
 

Writing foldit scripts.

FoldIt scripts are simply a way to automate one's manual action.

a simple script to do a global wiggle for 20 iterations is:

do_global_wiggle_all(20)

By adding other function you can combine other steps.
I'll write more about this tommorow.

Playing FoldIt takes time

OK, I've been playing FoldIt for nearly two months now.  I'm doing pretty well even if I'm still learning.  It's hard separating game playing from the science.  I'm mostly using scripts to get points and letting the science go except as needed to gain points.

Many  puzzles get good score for beginners by using:
Show Allignment
Select best.
Repeat:
  Shake Sidechains
  Short burst of Wiggle Backbone
Repeat:
  Wiggle sidechains
   Slightly longer burst of Wiggle Backbone
Run Tlaloc's script Hydrophobe
Run Tlaloc's script Cataclysm
Run Tlaloc's script Repeat Settle
Run Rav3n_pl's Walkin' Rebuild

Some of the science comes later.

Getting Started with FoldIt

I learned about FoldIt from the  University of Washington UWeek online magazine.  The article talked about a new article published Aug. 5 in the journal Nature describing how game playing can help science.  I thoght I'd give it a try.  It's not like other games but it's fund and there is a lively community of people.  I've been folding since then.  You can see my player entry and follow my progress as I learn the ropes and share them with you. If  I can fold proteins and help science while playing a game so can you.