Rebuild attempts to find a better shape for a section of your protein by trying the shapes of similar proteins. Although Rebuild is similar to the newer Remix tool, the two tools use different strategies. A 2016 Foldit blog post "Remix and Fragment Insertion" describes the difference between the two tools.
Both tools work with "fragments" of three segments. Rebuild works by looking in its database for fragments with similar amino acid sequence. The shape of matching fragments is applied to the protein being worked on.
Rebuild is a notoriously difficult tool to use manually. It can, however, be the key to significant scoring breakthroughs, particularly in the Middlegame. Most often, it better to use a Rebuild recipe, such as Tvdl enhanced DRW 2.8.1.
(As described in the 2016 Foldit blog post, an improved user interface has made it much easier to use Remix manually.)
Secondary structure is an important factor in rebuilding.
You can rebuild with bands .
The explanation given by the Baker Lab describes how to perform a manual rebuild in the original Foldit interface:
- You can access rebuilding through the right-click (or control-click) wheel menu in pull mode. Rebuild will search through completely new shapes for the protein's backbone. Use locks and bands to control the rebuild!
- The program looks at the selected sequence, looking at which amino acids and secondary structures are present, and builds a fragment library based on this.
- The program picks a random subsequence of 3 continuous segments in the selected region and inserts a cut at one end of the selected region.
- The program then does a look up into the fragment library for protein fragments that have similar AA and SS to this 3 continuous segment sequence and selects one.
- The program then copies this segment onto the current protein.
- The program applies an algorithm called CCD to get the new endpoints of the cut close together, and then closes the cut.
- If the protein is messed up badly (scores poorly) it resets back to the original shape.
- The process begins again at step (2).
- Using rebuild without locks or rubber bands produces a wide variety of different shapes, most of which will score very low due to clashes. This phenomenon is not completely random, although it will probably appear that way, even to very advanced users. Player Fugofish recently visited the developers and asked specifically about this effect. Here is her description of the response:
- When you select an area for Rebuild, Foldit scans a local database for the relevant sequences, as well as the structure you have given that sequence. So, when rebuilding a helix, for example, Foldit tends to cough up helix solutions more often than random loop sequences. Useful to know.
- On the other hand, using loops for rebuild tends to create the least secondary-structure biased results. This can be useful in, for example, having the database search decide where the backbone should turn for you.
It is important to watch the progress of rebuild, however, as a player with good intuition may recognize that one of these low-scoring shapes nonetheless has great potential if the clashes can be resolved. A player with a good idea of where an element "needs" to go (e.g. for packing the protein) can also use rubber bands to constrain a rebuild in that direction. In either case, following a rebuild, it will usually be necessary to resolve sidechain clashes (with a Shake for example), to local Wiggle the rebuilt shape, and then to global wiggle or Nudge the protein in other ways to reach a satisfactory Score.
Previous rebuilds are saved in the undo list, and you may return to them by clicking back through it. This is often useful, as the rebuilds can cycle through very quickly otherwise.
Feet1st has provided a useful YouTube video giving some idea of how Rebuild works, although its functionality has changed somewhat in the meantime.
One effective rebuild technique is to normalize a Helix, then freeze just that helix. Next, global Wiggle the protein. It will adjust into place around the normalized helix. Complete this combination after the structure has reached Stability by unlocking the helix and doing another global wiggle. You may get even more points. This technique works best if the helix is deformed to begin with, and if correcting it will result in a global score gain.
A second rebuild technique is to find a section which looks slightly out of place, convert it to a loop, freeze 3 segments, and rebuild. If there is an immediate point change: stop, shake, and global Wiggle. Usually expect this to lower your score a few points. Move to a bordering section and repeat. Points usually arrive at the 2nd - 3rd section, though it's possible to do this with 5 sections and get points on a long loop The identifying feature of this technique is the speed at which rebuild finds an alternate shape -- it changes almost before you can get to the stop button.
Note: In selection interface, a "real" rebuild must be at least 3 segments but the tool works for less.
Rebuilds are much more useful if you can follow these tips. Trust me, I thought Rebuilds were just a pain, but if you do them then you can get a ton of points. First you view coloring to see where the red is. Then, you lock two sections so the red is in the middle of the locks, or in any random spot you want to rebuild. Next, you right click and Rebuild. Stop the Rebuild right away so you aren’t loosing 1000’s of points. If the Rebuild is too fast then you can always undo it and go back to the spot you like. After that, you do a Global Wiggle, not a Local Wiggle. Then, you do a Global Shake. Lastly, you do a Local Wiggle after the Shake. Hopefully this helps, and if you need any other tips on Rebuilds, please contact me (cheese) on Fold It. I have a ton of more strategies with Rebuilds so contact me for more!