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kinetic's picture
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I breezed through the introductory puzzles, but they mostly involved using the functions like shake sidechains, wiggle, etc. Then I thought I'd try the beginner's puzzle (potato multicystatin), but it's completely different and I don't understand. It seems to entirely consist of aimlessly dragging uncooperative bits around to match the grey guide that just gets in the way and means I can't see what I'm doing properly. I don't see the point - I can see where I want to put everything, I just can't get it to go there. So it just seems to be a pointless exercise in mouse control or something. Aaaaaaarrrgh.

kinetic's picture
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OK I've calmed down now. But

OK I've calmed down now. But seriously, how do I move one bit without the whole of the rest of the chain shifting and without having to freeze everything? I'm going to do the intro puzzles again. I never did figure out what those purple things do...

kinetic's picture
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x

Cross-posting! Yeah rebuild, I didn't quite take that in either...

kinetic's picture
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I think you should be a proud geek

since you know what an irc client is and I don't!
Cheers anyway!

Joined: 09/18/2009
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Or...

...pidgin.
It is similar to ICQ.

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Mibbet...

...sounds interesting.
Does it work with the browser?

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hm...

Would be good on this PC (from my gf).
At home, I use pidgin, because it can use ICQ & co at the same time, and I don't need an extra account.

To my opinion, they should exclude the chat from the game window, it has some flaws.

Joined: 09/18/2009
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Right...

...if the chat would run in an extra window, it would run in an extra task-slot.
You could change its priority via task-manager, or minimize foldit, if you want to chat.
Even people with one-core-CPUs would benefit from that.
My PC (built out of spare parts from 3 PCs) has got some extras, but it is relatively old and has only one core, but foldit uses more than 2. CPU is always busy at 100%.

Do you mean the floating text like "good hydrogen bonding", and the scores?

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;)

Yes, this text is okay :)
They should give a GUI option to deactivate floating text completely or disable it if a script runs.
The script itself can give some output.
Those animations also take some CPU power.
In general, I have the feeling that the game does behave a little bit wasteful with ressources, or there is a leak.
See, a puzzle consists of about 100-200 segments (internally double as much, not counting sidechains), uni-coloured textures, no bump mapping, anti-aliasing, reflections or something like this.
Even those OpenGL windows screensavers could render such kind of graphics relatively quickly in the 90s.
Do you remember this screensaver with the tubes?

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rna

are there rna puzzles in there? or is it just protein?

kinetic's picture
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*computer stuff sails over my head*

I think what's causing me problems is that the beta sheet strands are twisted and I can't untwist them. I just want to pick them up and do it with my fingers. There should be a button that says "straighten out sheet regions". It's infuriating!!!

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Straighten out

You can straighten out them, using the new inteface (GUI)
double-click on a sheet, it should be marked completely blue, and some arrows will appear.
Above the arrows, there is a knob, which you will have to keep pushing.

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Picture

Look, I marked the knob red.Knob for straighten out sheets: Shows up if a sheet is  selectedKnob for straighten out sheets: Shows up if a sheet is selected

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levinthal, there is a tool

levinthal, there is a tool that allows you to straighten sheets. But you have to be careful how to use it and often rebuilding the entire sheet is a better option.

Straightening sheets:
If you are in original interface mode, right-click on the sheet, select "Tweak", then click and hold on one of the purple balls and wait until your sheet is normalized.
If you are in selection mode, double-click on your sheet so that the sheet and the surrounding loops are selected, then proceed as above.

Note that straightening a sheet often causes the surrounding loops to be twisted and getting low in score. These regions have to be rebuilt manually afterwards.

Rebuilding sheets:
In original interface mode, right-click on your sheet and press "Rebuild", in selection mode you would double-click the sheet and then press "Rebuild". Wait until a sheet is generated that does not have the twists in it that you wanted to remove.

kinetic's picture
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GUI interface? :-?

OK I'm clicking on purple balls but nothing is moving. clicking on the arrows makes the whole sheet rotate a few degrees...

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Regarding straightening helices and sheets...

One common reason that nothing moves when you hold down the purple button is that the loops attached to either side of the structure you're working on are too short. This is because the procedure for straightening those structure work by bending the amino acid residues as necessary-- and if there isn't enough space as "cushion," it might be impossible to do so.

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Yes...

And above these arrows you use to rotate, there is a knob (purple balls).

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Script

I'm just creating a script to do this.
At the moment, we can't download them, but past them as text.

kinetic's picture
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scripts

are also lost on me I'm afraid :-) Don't worry I have made some kind of breakthrough with freezing and rebuilding...

kinetic's picture
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Nope

I dragged everything so it perfecly overlaid the guide, rebuilt a few bits to tidy them up, made loads of hydrogen bonds, cemented it with purple bands, then did shake and wiggle and it just tries to fling itself apart again. I'm giving up before I trash the computer.

kinetic's picture
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So where does the human come into it?

I thought the whole point of this was to use human intuition. Well my human intuition sees four beta sheet strands with loops in between, and I just want to flatten them out, line them up in an antiparallel sheet and THEN think about wrapping it round the helix in some way without pulling the strands apart. But I can't untwist the strands or snap them together because it won't let me. Asking the computer to rebuild a strand until it looks the way I know it should (although it never does) seems to defeat the whole object of this. So I guess it's a game for computer programmers.

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Re: "I guess it's a game for computer programmers"

Levinthal:

I can understand your frustration here-- even as someone who has been playing this game for 1.5 years, I still see many cases where very creative methods are needed to restructure the strands/helices the way I want them to. The main reason the problem you're observing exists is that, by default, the program ensures that the residues stay together (i.e. the end points are fixed unless you're working with the termini). In other words, the reason that you can't bend a structure in a certain direction in some cases is because it's physically impossible.

Now, since we're working with a simulated structure in computational terms, a possible technical workaround is to relax the constraints during the intermediate steps and only require that the final structure fits the constraints. This is actually a feature in Rosetta (the software suite used for protein structure prediction/design that's also adopted in a simplified form in Foldit)-- "cut points" may be inserted between which two residues to temporarily allow them to separate (and be processed individually) and then rejoined later. The challenging part, however, is implementing this in Foldit as well.

==> See, the crux of the issue is really that what we want to do with the protein as humans can be difficult to program. After all, you'll have to first find a way to translate what you want to do into operations involving residues and atoms (translate or rotate in a certain direction while fulfilling certain constraints) AND ensure that the code works the way it's intended... which is easier said than done (and I'm saying this from personal experience, having worked with the C++ code of Rosetta in the past). Foldit, after all, is a computer program-- the protein puzzles are not produced as a physical toy, a model kit that one can play with bare hands.
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* That being said, here are a few hints that you can try regarding your specific questions:

1. In general, if a structure won't rebuild, consider setting several of its neighboring residues to loop temporarily and including them in the process; adding bands might also help. For your information, what rebuilding does is called "fragment insertion" in technical jargon-- basically copying short segments from a database of actual proteins based on the secondary structure and trying to fit them into the space that's available *given the end point restrictions*. Hence, the most common reasons that rebuilding doesn't achieve what you want even after many tries are (a) the segment you're rebuilding is too long (i.e. too many variations to try from), or (b) the resulting structure is too energetically unfavorable to be acceptable, or (c) no structure from real proteins can reasonably fit into the space given. If it's (a), rebuilding shorter segments one at a time might work, while if it's (b) the solution might be dialing down clashing importance temporarily.

==> But if it's (c), you're in trouble because that means extra pre-processing is required. If you're rebuilding something into a helix but can't, it's probably because there is too much space between the two end points; with beta strands, it's probably the opposite. And if you're trying to untwist a beta strand but can't, your best bet is probably restructuring it the hard way-- namely, going into full-atom mode, banding the needed atoms, and then rebuilding 3-4 residues at a time along its length. And if that doesn't work, try freezing everything except for those 3-4 residues, applying bands of strength 10 (first apply regular bands, then create a simple recipe that sets all bands to strength 10 automatically), and then wiggling. The backbone score will most likely drop by the thousands, but at least it will twist in the direction you want it too (remember, you can always fix the backbone later through local wiggling, etc.) For best results, clashing importance could be dropped to 0.10 or even 0.01 as necessary.
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2. One common reason that the protein falls apart is that it's too energetically unfavorable. Once again, this is why wiggling at clashing importance 0.01 + using bands to keep certain parts of the structures together is so important-- because it allows you to first fix the worst clashes partially. [For your information, wiggling is known as "gradient-based minimization" in the technical jargon. In other words, the program will move pieces around based on the direction(s) that gives it the greatest increase of score relative to the extent of transposition made-- which, unfortunately, sometimes means exploding the protein and missing the best structure. Wiggling at a lower clashing importance may solve the problem by first turning a -10000 clash into a -500 clash, which is much less likely to be so overwhelming that the rest of the protein must be sacrificed to fix the most energetically-unfavorable parts.

==> If that still doesn't work, you want want to freeze most of the protein and wiggle them (again, starting at clashing importance 0.01 if necessary) one part at a time. For the record, this issue is actually far more likely to occur when you're playing with guide-matching puzzles or those that involve threading, and the chance approaches one as the number of residues increase. If you're not trying to match a specific guide, extreme clashing is less likely to occur-- but when it does, remember that you don't have to follow the default option of doing a global wiggle with clashing importance set to 1.0. The option to decrease clashing importance is there for a reason-- in fact, that tool was vital in my attempt to swap two adjacent sheets in Puzzle 165, which is mentioned on Page 17 of the supplementary information section of the recent Nature article ( http://www.nature.com/nature/journal/v466/n7307/extref/nature09304-s1.pdf ).

* Bottom line: when what you're trying to do doesn't work, experiment with creative use of the tools. Unfortunately, this could mean a steep learning curve as such tactics often need to be discovered on your own (because they would be too complex for intro puzzles)...

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Stuck on introductory puzzles

If I stop working on the introductory puzzles how do I get back on to complete? And how do I go back and review/practice as I'm slow to learn the basics?

This looks like great fun but I'm obviously not saavy navigating this game yet. Thanks

kinetic's picture
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@infjamc

Thanks for the detailed reply! I got frustrated as I just didn't know where to begin with all those bewildering options and strange tools that are thrown at you in the beginner's puzzle. It made Microsoft Excel look like some kind of meditative aid. Sorry for being so grumpy, I have absolutely no patience at all. Hence why I got out of protein folding research! Anyway I might take some deep breaths and try again. :-)

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Patience

Well, this game needs much of patience, then the rest comes by itself.

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2 more things

There are some people, who have the opinion, that you have to be a programmer to play this game.
Like vixynn said before, you don't need to, because:

1.:You can drive (operate) a car without knowing how to build one.
2.:It is good to know how to make a script, but even if you don't know how to, you can use them or change some parameters. Everyone who can make an annual tax declaration (which is also filling some values into a form), can change a script.

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Agreed on patience

Kinetic,

Crashguard hit the nail on the head. You have to be patient to learn this game. It's not for the faint-hearted or the overly hasty. There are many things that need to be learned, and it simply can't be done in one quick gulp. even for many of us who've been doing this for a couple of years, there's always something new to learn. It took me a month to get a basic handle on the game, and there were far fewer options then...Don't give up because you can't master it in a week.

And yes, there's always some frustration at not being able to do what you can clearly see with your mind's eye. Some is a natural limitation of Human-computer interactions.

Also, don't forget to talk in chat. There are often people there who can offer on-the-spot suggestions and underlying method/philosophy to help guide your learning process.

You really don't need to be a programmer to play and you don't need to use scripts to have fun. I don't use scripts, except for a couple of primitive ones I use to do cleanup and I believe there are still other veteran players who either don't use them or only use them sparingly.

good luck!

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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