Time | Name | Message |
---|---|---|
12:32 | David | Hello everybody this is David Baker |
12:33 | spvincent | Hello Dr. Baker |
12:33 | MellyLam | Hello! |
12:34 | Lazarus | -uk hi David |
12:34 | Christoph | hi! |
12:34 | CharlieFortsConscience | :) evening |
12:34 | David | how are things going with the CASP targets? |
12:35 | Aotearoa | omg this is so awesome |
12:35 | CharlieFortsConscience | it's a lot of hard work |
12:35 | Lazarus | -uk you are probably in a better position to tell us how it's going Dr.B |
12:35 | Aotearoa | they have been challanging for sure |
12:36 | David | we are very excited about the mini-CASP results you came up with! |
12:37 | Aotearoa | phew ! i was worried about those as we hadnt had a lot of feedback, so were getting the hang of it? |
12:37 | spvincent | In the R@h forums some time ago you said that people were better at folding than 1 computer but not as good as 40,000 (or something). |
12:38 | Lazarus | -uk hopefully 'all-hands' will be able to refine some of the solutions still further |
12:38 | David | there certainly are cases now where foldit players are doing better than could be achieved even with very large amounts of computing power |
12:39 | David | "all-hands" could be very powerful, but it also could have a pitfall that everybody needs to know about |
12:39 | spvincent | What would that be? |
12:39 | David | in general, we see players sometimes "piling up" too much at the best current solution |
12:40 | CharlieFortsConscience | *walked to death*? |
12:40 | Aotearoa | it's been great to see the new folders performing so well. aap, cfc and Keypad5 ... so many new ones have realy changed the way we fold. |
12:40 | Lazarus | -uk we may be refining the wrong solutions |
12:40 | mat747 | cfc is right |
12:40 | David | it is like gold-mining when everybody starts searching around the best current find |
12:40 | David | but the mother-lode is somewhere else which hasn't been discovered yet |
12:40 | spvincent | Perhaps you could have them as sepearte puzzles then |
12:41 | Aotearoa | more re-starts then david? |
12:41 | David | so in all hands you need to consider not only the best current solution, but the full range of solutions presented, and also keep exploring on your own |
12:41 | Lazarus | -uk is there any way your team could search out the most likely candidates, rather than the highest scoring ones |
12:41 | beta_helix | Aotearoa: yes... we are also excited about the new crop of top folders. As for the mini-CASPs, David already mentioned this great case where we were impressed by how you all used the alignment tool:http://fold.it/portal/node/987564 |
12:43 | David | the real problem is that computers currently aren't good at detecting which are the most likely candidates. |
12:44 | David | once you get very close to the solution, the computer can tell because the energy is very low (the score is very high). |
12:44 | Aotearoa | the alignment tool does throw up some crazy template configurations though, with prolines in the middle of sheets and helix's. i dont know if leaving them there is good or bad |
12:44 | David | one of the hopes is that people could be better at deciding what is a likely candidate |
12:45 | David | we could try to decide with are the best candidates, but one of the goals of the casp foldit experiment is to try to avoid "expert" intervention as much as possible |
12:46 | Lazarus | -uk that may be where scoring actually becomes a problem. pulling everyone towards the points and away from the correct solution |
12:46 | CharlieFortsConscience | So we're still ahead in the 'it doesnt look right' factor... |
12:46 | Lazarus | -uk so, we just have to do our best |
12:47 | David | yes--you are absolutely right. the computer has this problem even worse, though--it has no intuition about where things might go so it has to be greedy |
12:47 | spvincent | I sometimes wonder if these scripts we're creating are doing no more than a very bad and ineffecient Rosetta@home |
12:48 | David | I think your scripts and approaches are much more interesting than that. you are coming up with new algorithms that we never imagined |
12:48 | spvincent | Good! |
12:48 | BletchleyPark | good evening David, do you see a role for GPU computing within foldit ? |
12:49 | David | yes-you are very far ahead in the "it doesn't look right" factor! and hopefully as you get more experience this will just keep increasing |
12:49 | CharlieFortsConscience | We react to the constraints placed upon us, and find shortcuts that make sense to our style of play... |
12:50 | David | I think GPUs could play a role--it is really a question of manpower. we are hoping NVIDIA will help us out here... |
12:51 | Aotearoa | we sure could do with a new influx of folders and material we know is "correct" to teach them more |
12:51 | beta_helix | so more quest to the natives? |
12:51 | Aotearoa | *omg please NOooo!* grin. |
12:52 | spvincent | I don't find those puzzles much fun |
12:52 | mat747 | me too |
12:52 | aap2 | i kinda like them |
12:53 | David | we could set up simple puzzles where you are given some number of models including the native and just have to pick out the native? these would probably be easy and not time consuming. |
12:53 | CharlieFortsConscience | Hmmm... FoldClub has changed so much in the last year, more longer lasting beginner puzzles would help keep newbs around. It's a lot more technical, and scary than it used to be |
12:53 | Aotearoa | That sounds good |
12:54 | David | what do you think of the design puzzles? |
12:54 | spvincent | That would be fine. I think you did that once. |
12:54 | CharlieFortsConscience | :) I personally like them. A lot. |
12:54 | MellyLam | good point CFC. The puzzles are a lot bigger and slower than they used to be, and they take a long time to work out |
12:54 | Aotearoa | design puzzles GREAT David, but we still have to change our limited thinking to research topics and interests to make them stronger. but we need more and more |
12:54 | spvincent | I don't really know I'm doing with them and end up trying things at random |
12:54 | Aotearoa | *pletsch and I would like to use fold.it and take on some projects.* |
12:55 | BletchleyPark | @David: are there collaboratins between the various ' folding' initiatives ? (GPUGrid, Rosetta, FAH come to mind) |
12:55 | beta_helix | we can post beginner puzzles with natives to get new folders to learn the alignment tool (and for you all to practice with them?) |
12:56 | David | to get a feeling for protein interactions and binders, it could be useful to browse the protein structure database which has a free viewer |
12:56 | Aotearoa | Yes Beta !! great idea. |
12:56 | beta_helix | here is the protein structure database for anyone who hasn't been there: http://www.rcsb.org/pdb/home/home.do |
12:56 | Aotearoa | i've noticed more feedback from beginner puzzles than competition puzzles |
12:56 | aap2 | i think i learned alot from the qttn puzzles |
12:57 | David | there are some collaborations on the science side. for example, we are collaborating with some of the FAH researchers now on looking at protein folding kinetics using Rosetta and Rosetta@home |
12:57 | beta_helix | our hope was that by seeing the native, you would be able to see what moves are needed using the alignment tool |
12:58 | BletchleyPark | that sounds like a good initiative to me, they also have GPU experience. GPUGrid sells / licenses its GPU engine |
12:58 | David | we are very excited now about our designed flu virus binder. |
12:59 | Christoph | have you already tested it in the lab? |
12:59 | Aotearoa | GREAT !!! |
12:59 | Aotearoa | Vakobo are you here? |
12:59 | David | we are starting up projects to design binders to other pathogens, and after CASP we hope to get all of your help with this! |
12:59 | Aotearoa | <--- I'm in. |
12:59 | spvincent | Will the CO2 fixation stuff be in FoldIt too? |
13:00 | David | we know that in a test tube the designed protein binds tightly to the flu surface protein. we don't know yet whether the protein can actually block flu infection |
13:00 | Aotearoa | question: do out puzzles on their "paths" to final protein shapes, get included in your final results. |
13:01 | David | we can set up the CO2 fixation problems as foldit puzzles as well |
13:01 | spvincent | Neat |
13:01 | BletchleyPark | @David: is there a limit on how big the fold.it proteins can be ? |
13:02 | David | the only size limit is that manipulations get slower and |
slower | , as you know. we are working on speedups now | |
13:02 | BletchleyPark | very good to hear ! I notice that foldit uses a lot of ' ordinary' floating point math, might be good to make it SIMD aware ? |
13:03 | beta_helix | Aotearoa: those in the Baker lab working on design look at all the foldit solutions, filtering them using different methods |
13:03 | Aotearoa | ty beta: I ask that question because I can go through many different combinations which are low scoring shapes/combo's and various designs but "dont" save them as I go through a range of differing shapes. |
13:03 | David | we are now trying to figure out how to get bacteria to grow and make fuel molecules from solar generated electricity and CO2 |
13:04 | David | this would be the ultimate in "clean energy" |
13:04 | Aotearoa | I saw some Ideas from BMW ag in Munich when I was working there David |
13:04 | David | the first challenge is to figure out what enzymes are needed, then we can set up design puzzles to make them |
13:04 | spvincent | Something like that's going to be really needed if the world's going to be fit tolive in. |
13:05 | CharlieFortsConscience | We hear rumours that Nature will publish soon... how is that going? Back from review yet? |
13:05 | CharlieFortsConscience | We hear rumours that Nature will publish soon... how is that going? Back from review yet? |
13:05 | David | yes--it is a super hard problem but something like this has to be done! |
13:05 | David | I expect to hear from Nature any day now--you will be the first to hear! |
13:06 | Aotearoa | *my goat will be very happy to hear that* |
13:06 | Aotearoa | *lol j/k* |
13:06 | David | It is looking like they will do a news article in their front section about game playing and then have the scientific article describing your amazing results in the main part |
13:07 | David | we are getting a huge boost for casp and inhibitor design now by the recent increase in participants in rosetta@home--I hope it lasts! |
13:08 | BletchleyPark | Nature article may spark interest of the Discovery Channel, that would reach quite a few people who may turn out to be players |
13:08 | David | yes-that would be great! |
13:09 | Aotearoa | we realy need a few of us to stop folding for a while and start writing how to use the new interface and how to fold using aap kp5 and the other new folders methods dont we. we are starting to get behind in the wiki updates |
13:09 | David | back to CASP--for problems where the alignment is less good (fewer identical residue pairs), definitely keep in mind that the alignment could be wrong |
13:09 | David | particularly in edge beta strands which are frequently misaligned. |
13:09 | David | for these it could be good to shift left and right one residue at a time |
13:10 | beta_helix | Aotearoa, after CASP (if you all aren't too burnt out) that would be great |
13:10 | spvincent | Do you mean that these are good candidates for register shift? |
13:10 | Aotearoa | I would like to sugggest a new tweak view and tool for helping with that ! will write it in feedback sooner than later. |
13:10 | BletchleyPark | You could send a copy of Nature with some background info to Pioneer productions and see if it sparks interest with them |
13:10 | David | yes! I would focus register shifting on the edge beta strands. doing it at the alignment level shoudl be particularly powerful |
13:10 | BletchleyPark | They do a lot of features for DiscC |
13:10 | Christoph | instead of trying out different alignments, couldn't we simply rebuild those regions? |
13:10 | Christoph | at the end of strands |
13:11 | David | that is worth trying as well-but I would first explore different registers |
13:11 | CharlieFortsConscience | I keep using the phrase 'alignment is just a gift-wrapped head start' - surely the pt gains come with the post threading rebuilding? |
13:11 | David | remembering that regions with strong sequence identity should not be altered |
13:12 | BletchleyPark | @David: is the alignment score holy ? |
13:12 | David | yes--the posthreading is critical-BUT you need to start with the right alignment |
13:12 | David | no--it is not holy. treat it as a rough indicator |
13:12 | Aotearoa | im having problems counting the segments to move the right ones |
13:12 | BletchleyPark | ok, t hanks |
13:12 | Aotearoa | numbers at the top would be nice |
13:13 | David | this is like being in my lab and talking about ten different research projects at the same time! |
13:13 | beta_helix | Aotearoa, we will add numbering to the alignment tool soon! |
13:13 | CharlieFortsConscience | Is it worth then, pursuing a highest thread score? |
13:13 | Aotearoa | *ty beta* |
13:14 | David | it is probably worth trying different alignments, quickly fixing them up, and then making a call about which are worth pursuing |
13:14 | David | maybe the different alignment shifts could be divided up among team members? |
13:15 | Aotearoa | once we have threaded a protein, then made changes. can the Thread (top line) then reflect those changes ? |
13:15 | Aotearoa | *reverse engineer* |
13:15 | CharlieFortsConscience | *...quickly, is a judgement call, with us Luddites on slower technology... but I see what you're suggesting* |
13:15 | David | computers can't solve the problem because again they can't "look ahead" and determine what are the most promising avenues to pursue |
13:16 | BletchleyPark | Has alignment scoring been studied or is it based on assumptions ? |
13:16 | David | yes, it has been investigated, but all scoring schemes are approximations. the reality is the energy of the 3D structure |
13:17 | BletchleyPark | ok |
13:17 | David | I meant "alignment scoring schemes are approximations" |
13:17 | beta_helix | Aotearoa, that would be a bit more complicated... but an iterative thread tool would be a cool idea |
13:17 | BletchleyPark | I understood it that way, thank you |
13:18 | spvincent | Is the energy function finalized or are are small improvements continuously being made? |
13:18 | David | we are constantly working to improve the energy function. |
13:18 | David | we are making slow but steady progress I think |
13:18 | Aotearoa | each puzzle seems to reflect that score differently spvincent. |
13:19 | Aotearoa | its way better than its ever been david |
13:19 | Christoph | are we getting the improvements made to rosetta and rosetta@home in foldit too in regular updates? |
13:19 | David | yes. everytime you have to update foldit you are getting the latest improved version |
13:20 | BletchleyPark | Are the critical routines of the foldit software hand-optimized or is this compiler code ? |
13:20 | Aotearoa | *geek alarm* |
13:20 | BletchleyPark | No, pro alarm |
13:20 | Aotearoa | lol *j/k* |
13:20 | BletchleyPark | This is my profession |
13:21 | David | the core algorithms are all the Rosetta C++ code, similar to what is running on rosetta@home |
13:21 | BletchleyPark | is that open source by chance ? |
13:21 | David | the rosetta code is free to everybody not trying to make a profit |
13:22 | BletchleyPark | great, I'd love to improve it |
13:22 | phryll | yeeeah boooy |
13:22 | David | we charge companies licensing fees, and use this to support the rosetta developer meetings |
13:22 | phryll | :D |
13:22 | aap2 | what if you just happen yo make profit? :P |
13:22 | Aotearoa | BP - pletsch and I are looking for work. <--- no qualifactions but we will fold you anything from cakes to alien lifeforms for you or your clients. FYI. |
13:22 | BletchleyPark | shirts too ? :) |
13:22 | beta_helix | any last CASP related questions for David? |
13:23 | CharlieFortsConscience | I mentioned earlier, FoldClub has experienced a huge evolution in the last year - what plans do you have for us in the future? Any blue sky plans you can tell us, or are we in a consolidation phase... |
13:23 | phryll | ARE YOU N.E.R.D.S.? |
13:23 | David | companies have to pay |
13:23 | BletchleyPark | can we be fed one full CASP puzzle (a big one) ? |
13:23 | Aotearoa | I would just personally like to say, Thank You David Baker ! you have realy had a big impact on my life. |
13:23 | Christoph | there's one with 800 residues I think.. |
13:24 | BletchleyPark | I'd like a go at that, just to see where we can take it |
13:24 | David | things are happening so fast with rosetta and foldit it is hard to predict where things will be in a year |
13:24 | Christoph | http://predictioncenter.org/casp9/target.cgi?id=49&view=all |
13:24 | Aotearoa | I'de like to try them all too. even if we do fail, good to make a massive helix and band it up. |
13:24 | beta_helix | the 887 residue CASP9 target that was released yesterday is not a single domain |
13:24 | phryll | IMAGE: |
13:25 | David | big proteins we chop up into domains. |
13:25 | David | the problem with really big domains is that for most people's computers they would be painfully slow |
13:25 | BletchleyPark | maybe as a test puzzle ? |
13:26 | Aotearoa | Asteria is my new wife (computer) She's keen to try some funky stuff. |
13:26 | CharlieFortsConscience | *phryll, restart and follow the tips closely. And welcome to FoldClub* |
13:26 | David | there are so many targets we don't want to waste your time on problems which would be very frustrating |
13:26 | aap2 | perhaps a very big puzzle that doesnt get calculated into the global score? |
13:26 | beta_helix | CFC, I think we lost phryll |
13:26 | spvincent | I doubt if my Mac Miini could handle that.In fact I'm sure it couldn't |
13:27 | CharlieFortsConscience | *shame* |
13:27 | BletchleyPark | I think we're keen on bumping into that performance waal just to see where it is. |
13:27 | Aotearoa | true. we can do that when we've found more cures for things for biofuels and H1N1 important things. |
13:27 | BletchleyPark | wall |
13:27 | David | I always hope that what we do each year would have looked "blue sky" the previous year-one reason I don't like predicting the future! |
13:28 | David | we could post big problems as test puzzles to test equipment on |
13:29 | BletchleyPark | I'd welcome that |
13:29 | Aotearoa | we need a TEST area for crazy stuff like that - perhaps on BETA login not MAIN |
13:29 | beta_helix | we could put a huge CASP target in BETA for you to try out... |
13:29 | Judecca | im getting a new laptop soon so i would be interested in seeing how well it handles a larger protein. if anything just to benchmark it |
13:29 | David | I'm getting hungry--any last questions before I go find something to eat? |
13:29 | beta_helix | exactly, Aot, good call |
13:29 | mat747 | david - i think some video`s on the different subjects in wiki would help, like register shift , things we are doing well on and not some well that. things you would like us to try . |
13:29 | BletchleyPark | @beta_helix, please do, sounds interesting |
13:29 | beta_helix | will do! |
13:29 | Judecca | beta would be a good idea for that, heh maybe add an option to show FPS |
13:30 | aap2 | some visual advice/input would be great |
13:30 | beta_helix | we can easily add FPS |
13:30 | Aotearoa | What are you going to Eat David? your own lab made proteins or something like KFC ? |
13:30 | spvincent | Written stuff works better for me : not videos |
13:30 | Aotearoa | *don't answer that btw* |
13:30 | David | mat: we will be watching and try to give advice and pointers as things move ahead |
13:30 | CharlieFortsConscience | ...we grumble, and we rank up occasionally, but we keep coming back every day. Thanks UW, for keeping us sharp. |
13:30 | mat747 | david - thanks |
13:30 | David | great to talk with all of you!! |
13:31 | BletchleyPark | Many thanks for your time ! |
13:31 | David | bye! |
13:31 | aap2 | bye |
13:31 | mat747 | spvincent - both would be good |
13:31 | spvincent | true |
13:31 | Aotearoa | yeah ! |
13:31 | mat747 | bye - david |
13:31 | Aotearoa | I waited for two years for that. |
13:31 | Aotearoa | today is the best day of my life. |
Maybe it is really better to launch multi-start-puzzles not in a single puzzle, but like the CASPs as a,b,c,d.
Many scripts use the reset/restore (very)best functions, and it is hard to handle with another starting position if you already have brought one of them to high score.
Crashguard, the reason we stopped doing a,b,c,d puzzles (and instead created the new alignment tool where you can load the different templates yourselves) is because in the other 2 chats players mentioned that there we too many puzzles already.
Right now we have 3 puzzles up, 1 template and 2 denovo CASP targets. If we gave you a puzzle for each denovo Rosetta model, that would be 11 puzzles up right now!
This makes sense.
Then it would be helpful to clear the "very best" result.
As Dr Baker said:
"in general, we see players sometimes "piling up" too much at the best current solution"
[...]
"it is like gold-mining when everybody starts searching around the best current find but the mother-lode is somewhere else which hasn't been discovered yet"
So, if you play a multi-start or all-hands, and you've reached high score, you can't go back to the middle, only by loading another solution.
Or ... you can, but if you did some mistake at tweak/nudging, you can't do a reset.
Let me give an example:
You have played a start position through, resulting a score of 11,000.
You take another start position and improve it, resulting 10,750 points.
Then, you do a wiggle, get 10,800p and try to nudge at a sidechain, but it is the wrong one, making the score go back to 10,700.
Now you can't reset to the 10,800 state, because "restore very best" would take the solution with 11,000 points. It is unusable in the second turn.
If you had the abilitiy to clear the "very best" result at taking another start position, this won't have happened.
Sure, there is the possibility to use the undo bar, but it only has a limited amount of states, vanishing fast if you use some scripts.
That makes sense Crashguard.
You would then save your 11,000 point solution, "clear very best" and basically start over, right?
We will try to implement this soon.
Until then, hopefully you can use the quicksave slots for that 10,800 solution before trying a nudge or something.
That's right!
At the moment, I use regular save and quicksave slots indeed, to try another starting position or other alignments.
Maybe it's best to be asked to clear the "very best" result if you reset the puzzle itself, this would give not so much problems.
Thanks in advance!
you could change the scoring: take a complex formula that takes into account major impacts on low-scoring proteins but also small progress on proteins rated high: a combination of % growth, progression and absolute final scores. The time we guess the algorithm, we will work on all solutions.