Foldit Wiki
Register
Advertisement

My preference was to dismiss the writing of this article, as several very good methods are already present on this wiki, however having been asked, I resort now to disclosing a step by step analysis of the means by which I fold proteins.

Early Game

To me this portion of the game is one of the most significant, as failing to achieve a good start at this point will severely hamper your ability to make important gains later. There are a couple of techniques which I find help with this significantly. At the very beginning of the puzzle, this is the starting technique.

  1. Wiggle until the score doesn't move for a while
  2. Shake
  3. Repeat steps 1 and 2 until no further gain is made
  4. Reset the puzzle
  5. Shake
  6. Wiggle until the score doesn't move for a while
  7. Repeat steps 5 and 6 until no further gain is made
  8. Restore Best.

The above steps will in many cases mean a difference of 100 points or more to the starting point of a puzzle. With some puzzles I have found the difference to be as high as 400 points.

After having found the starting structure with which we will be working, the next step is generally to do an inspection of the puzzle. Make a mental note of areas which stand out as being low yielding. Also look for portions of the puzzle which appear to be out of place. The following is a list of things which I look for:

  • Ends of protein, You will find that on many of the puzzles, in the optimal configuration both ends of the protein often appear right next to each other, often parallel for several segments before the end, in others they are still parallel, yet pointing off in opposite directions. If the ends are in random locations, consider that you may not have a very good starting structure, and perhaps take a look at others, or repeat the steps in the first section again. This is not an absolute (as far as i know) so don't base your whole strategy on this, jsut keep it in minde
  • Areas with multiple Phenylalanine and/or Tyrosine sidechains. These are the ones with hexagon shape on them, and tweaking them a bit to get the hexagons parallel to each other, often helps immensely.
  • Areas with Proline sidechains, as these almost never appear on a helix or sheet (sometimes at the very end of the helix) they are a good indicator of where the different portions of the protein start and end. Though usually not immediately helpful, it's good to get to know your puzzle a bit. Sometimes, this will make the difference one where i decide to try to bend the backbone.

Once the above areas have been examined and perhaps some basic pulls and adjustments made, it's time to move on to the mid game and begin really tweaking this thing.

Mid Game

Mid Game is where all the major points jumps come in, and the amount of time spent on mid game cam make huge differences later on. My progression through the mid game portion is generally as follows:

  • Smash and Shake: Drag portions of the puzzle into each other, particularly I focus most of this effort towards any helix, pushing it into the surrounding portions of the puzzle. Knowing how far to push is very subjective, typically I do so until both the side of the helix, and the area it was pushed into are red with little starts indicating clashes. Once it's there, shake. Now I tap the W key a couple of time briefly (no more than a second between taps) shake again, and repeat this a couple times, then let the puzzle wiggle out. If an improvement is made, keep it, if not, restore best. I find myself doing this over and over again for 10 - 30 minutes on any puzzle. Basically, keep at it until it becomes frustrating that you are dropping each time, rather than gaining.
  • Pull and Shake: After smashing fails to yield anything else, now it's time to try it's opposite, start pulling pieces apart a little bit, shaking and wiggling them back together. If the new score is higher, great, if not reset best. Also, take note of any sidechains which frequently change position while doing this, often I will lock these so that I can come back and play with them a little later.
  • Sidechain_Position: After the easy stuff no longer produces additional points, it's time to start manipulating this manually. If on this puzzle, I have locked sidechains from the previous step, this is the starting point for me, I will unlock them 1 by one, and try the different sidechain strategies already laid out in the Sidechain_Position article. After focusing on the locked chains, I typically go after the Tryptophan (hexagon with pentagon), the previously noted Phenylalanineand Tyrosine and the Arginine (very long squiggly one) trying to find better postions for them.
  • Just play with things a bit, this is a good time to try out Rebuild, Local_Rebuild_Strategy,Manual_Rebuild, or Tweak. This is also a good time to band pieces together to try to increase Compactness, and to get rid of Constraints. though I should stress, I keep these to a minimum, and typically only do them on extremely troubled areas, or after atleast two passes through with the above techniques do not produce satisfactory improvements.

It is important to note, any time your score increases, you should pull the structure slightly, not allowing it to drop more than about 100 points, and wiggle it back together again, do this several times until it stops yielding points. Doing this will add 2-5 points to each improvement you gain in most cases. After spending time on the mid game steps, I will typically either quit for the night, take a break, or move on to another puzzle. After coming back to the puzzle from a break it's good to go through the midgame steps one more time. It is important to get everything you possibly can before moving on to end game strategy.

End Game

Before moving on to end game it's important to go through mid game steps 2 or 3 times, typically I would not recommend doing the following steps until after the puzzle, is already the absolute best that you can make it.

  • Local_Wiggle_Strategy is one of the most effective techniques of boosting score. It is also for many people one of the most effective techniques for keeping them out of the top folders because they do this technique far too early. The reason is, doing this will greatly increase the Mojo of your puzzle and often prevent your from making gains with the mid game strategies. Once I am satisfied with the results of the puzzle, I will employ this tactic, first waliking the backbone from one end to the other in 4 and 5 piece increments, and then one more time in 2 and 3 piece increments. Sometimes if the final score is close, i may walk it yet again in 2 and 3 piece increments to gain a couple more points.
  • It is very important after the above strategy to pull and wiggle the puzzle several times after doing so stops yielding points.
  • Following the above, I will start at the end of a protein, lock a segment two off from the very end, and wiggle only the end piece. After wards move the lock up one, and repeat until moving the lock about 5 times no longer yields a gain. You can do this to both ends of the protein structures.

After the above end game steps have been taking, it's time to move on to another puzzle or work on a group solution, as i find the endgame steps make it nearly impossible to increase your score any further once the Mojo sets in.

Good Luck & Happy Folding!

-Steven Pletsch

Advertisement