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gronne's picture
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I find this project highly interesting, even if I haven't contributed personally yet. I'm just curious if it is, or really will, have any real scientific significance?

Has there been anything promising revealed so far?
If the results are promising, I'm positive there'll be a great amount of people joining, so I really think you should be clear on what the results are.

axcho's picture
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Thanks for asking.

Thanks for asking. :) Currently we are in the process of proving this, through our Grand Challenge puzzles. We're collecting data for a Nature paper about it (when I say 'we' I mean the biochemists on the team, not me in particular).

So far it looks like we are on track to build a solid case for Foldit's efficacy. Once we complete our analysis we'll definitely be talking about the results.

Blog post about it here.

Joined: 12/14/2008
short words

axcho, is it possible to have a few words on what a puzzle is thought to show and the result of it possible e.g. after closing it together with the video a conclusional text under the "This protein perfroms lipid binding operations in rice" (A really short one ^^)

That goes on the line of the simple question "why?". Its another point where the players are hanging in free air.

bobfin's picture
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Relationship to real protein dynamics

All Foldit contributors will be well aware of how easy it is for the protein to become trapped in a local energy minimum which although far from optimum (or more accurately the current highest score) it is never the less extremely difficult to nudge or perturb the protein into a new conformation.

I find it difficult to reconcile this behaviour with what must presumably happen in the cell where to be useful the protein would need to fairly rapidly assume its 'useful' conformation. If real proteins became easily trapped in local minima which rendered the protein inactive presumably functions in the cell would be compromised.

I accept that in the cell there may template proteins or molecules which may initially bind the protein and force a favourable initial conformation. But this begs the question if this is what happens how realistic is the Foldit simulation?

axcho's picture
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I'm no biochemist, but I'd

I'm no biochemist, but I'd imagine that there's enough bumping around going on inside a cell that any protein not in its lowest energy state would be unfolded again. Plus molecular processes happen very fast, so it's not like there would be a lot of idle time spent waiting for a protein to get into shape...

LennStar, the description text is written by the guy who posts the puzzles (beenen34). I can forward your request to him.

Joined: 06/06/2008
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Puzzle Purposes

Hi LennStar,

To answer your question, most of the puzzles we are posting and have been posting over the past few months are focused on determining where human folding intuition can out perform automated prediction algorithms.  The reasons we have for posting a puzzle may not be entirely related to the function of the protein, but rather to certain structural traits or issues that the puzzle we post has, so that we can see if the players can solve these issues.  This is the main focus of the paper we are working on, to find what protein folding problems exist where humans can outperform known algorithms.

Unfortunately, we can't release the particular purpose of each puzzle because it could taint results for future puzzles that we post.   I'll just have to ask that you be patient until we have finished running the puzzles and collecting our data for the paper, at which point we will publish what results we found.

On a positive note, after design mode is released, the design puzzles will have plenty of background information associated with it.  Each puzzle will be focusing on a specific protein design problem, and we will inform all of you as to what exact problem you're working on, and what implications a good solution may have, at the release of each puzzle.

Joined: 12/14/2008
"Unfortunately, we can't

"Unfortunately, we can't release the particular purpose of each puzzle because it could taint results for future puzzles that we post."

Thats what I feared. Very unfortunate.
Thanks for answering.

Toshi's picture
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Optimal Low Energy Level vs Minimum Low Energy Level

If I remember correctly, the function of many proteins is maintained by a conformational change of some kind. Although there may be a minimum low energy level for a particular protein, is it possible that the minimum low level is not the optimum low energy level from a functonal point of view? If it takes a lot of extra effort for the protein to untwist and rearrange itselt to arrive at the absolute low minimum energy level, why bother, if the structure will do the job and if it is going to turn around and go back to a different functional conformation. In other words, is it possible that function trumps energy minimums?
Proteins live in a constantly changing environment from an energy point of view. If you look at membrane potential; it is not static. Absolute homeostasis is not a goal for all cells or proteins If it was, our brain, nerves, heart and muscle cells would not function very well. It just seems that that the question of function is a very important one to take into consideraton.
So my question is, how do the computer models account for function? How do the scientists account for function in working on these problems? I just can't help but wonder about the process by which the "optimal structure" is derived. Maybe it is more important to be just good enough to get the job done.
I understand the idea of blind experimentation in order not to influence the result and that this is a game of pitting man against the computer algorithms to see if there is a way to improve the computer models. Maybe function is not relevent to these problems. The concern is probably with the approach to the problems; the thinking process. My concern is that it just might be missing the whole point.


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, Boehringer Ingelheim, RosettaCommons