Developer Chat
Thu, 04/19/2012
@betahelix | Hi everyone! We'll be starting the Double Scientist Chat in ~half an hour! | 14:05 |
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thealbatross | awesome! | 14:05 |
thealbatross | ...I'm going to have to miss it though :( | 14:06 |
frood66 | i do not put the game down here - only point out the obvious | 14:06 |
@betahelix | I am about to post the new Flu Puzzle so you can play around it for 30 minutes before the Scientist Chat: | 14:07 |
@betahelix | http://fold.it/portal/node/992416 | 14:07 |
MEFreed | Hi beta - yay new puzzle! | 14:07 |
thealbatross | awesome! | 14:07 |
frood66 | hi beta | 14:07 |
@betahelix | Hi gang! | 14:07 |
@betahelix | wait for it.... | 14:07 |
frood66 | not really | 14:07 |
@betahelix | ... | 14:08 |
frood66 | other puzzles end soon | 14:08 |
@betahelix | you still have 2 hours for 542, plenty of time ;-) | 14:08 |
@mimi2 | there speaks the non player :) | 14:09 |
frood66 | and little machines allow little extra | 14:09 |
thealbatross | 542 is a tough one | 14:09 |
thealbatross | I found a good alignment, but sealing those cutpoints is pretty tricky | 14:09 |
frood66 | beta - guess u will have to be 'beta' than that | 14:10 |
frood66 | for the 'little guys' - 2 hrs is a lot | 14:11 |
@betahelix | hahahaha... I was totally being facetious! | 14:13 |
thealbatross | heh heh | 14:13 |
thealbatross | I'm going to try out that new one... | 14:13 |
kristis | ? | 14:13 |
kristis | hey | 14:13 |
frood66 | i know what facetious means | 14:13 |
kristis | why everything is locked | 14:14 |
@mimi2 | we know - but you gave us the opportunity | 14:14 |
frood66 | not a good idea - i suggest | 14:14 |
frood66 | hi mimi | 14:15 |
@mimi2 | greetings and salutations | 14:15 |
frood66 | :) | 14:15 |
@betahelix | I know how hard 542 is, we will repost it soon with the "best alignment" and the native as a guide | 14:17 |
thealbatross | Ooooh.... | 14:17 |
thealbatross | good plan | 14:17 |
@betahelix | anyway... I will let you work hard on that (and check out the new Flu puzzle, 546) and I'll be back for the Scientist Chat in 15 minutes! | 14:17 |
frood66 | beta: u underestimate | 14:17 |
@betahelix | never! ;-) | 14:18 |
MEFreed | Quick - while beta is here, all in favor of hammer tool say Aye! | 14:18 |
MEFreed | :) | 14:18 |
frood66 | air hammer! | 14:18 |
MEFreed | (Dislike this protien very much) | 14:18 |
@betahelix | you mean the scissor tool? | 14:18 |
frood66 | thought u were gone lol | 14:19 |
MEFreed | Nope. Hammer. To murder the protien more violently than setting ci to 0. | 14:19 |
thealbatross | (heh heh) | 14:19 |
frood66 | nahhh - TNT | 14:19 |
@betahelix | hahahahaha... duly noted. see you soon. bye! | 14:19 |
thealbatross | later | 14:19 |
frood66 | well i'm still smiley | 14:20 |
frood66 | guess it's my problem | 14:20 |
harp | hi frood, hammer would be a most interesting addition to the tool kit, lol. I am in favor of it :-) | 14:22 |
MEFreed | It would be a nice way to talke out anger at a protoine. | 14:23 |
harp | with a caution: may cause major damage to computer xD | 14:24 |
MEFreed | Still probably less than a real hammer :) | 14:25 |
frood66 | hey harp | 14:26 |
harp | Would feel pretty good sometimes lol | 14:26 |
harp | hey how are you? | 14:27 |
frood66 | smiley now | 14:27 |
frood66 | *snigger* | 14:27 |
harp | sure about that ? | 14:27 |
frood66 | no happy thx harp | 14:27 |
frood66 | rewind.... | 14:28 |
mottiger | SCIENCE CHAT | 14:28 |
frood66 | happy - thx harp | 14:28 |
harp | k | 14:28 |
frood66 | 2 mins mott | 14:28 |
beta_helix | Hi everybody! | 14:31 |
MEFreed | Hi beta! | 14:31 |
frood66 | hey | 14:31 |
beta_helix | Please welcome DavidLa from the Baker Lab | 14:31 |
davidla | hello | 14:32 |
silverberg | hello | 14:32 |
MEFreed | hi davidla! | 14:32 |
@auntdeen2 | welcome, davidla | 14:32 |
beta_helix | He's working on the new way to fight to Flu: | 14:32 |
mottiger | hey david | 14:32 |
beta_helix | http://fold.it/portal/node/992416 | 14:32 |
frood66 | hey hey | 14:32 |
twisted1 | hi davidla hi all folders | 14:33 |
beta_helix | We just posted DavidLa's new puzzle if you have any specific questions about it. | 14:33 |
beta_helix | (Puzzle 546) | 14:34 |
mottiger | strange, i can log into all three puzzles | 14:34 |
spmm2 | is there a reason for the piece being bent or does it just come that way? | 14:35 |
mottiger | <15 <150 and open | 14:35 |
@auntdeen2 | I have a question... is it better to have bonds to the frozen piece or not? It seems that highest scoring solutions on flu puzzles are not the ones with the most bonds | 14:36 |
davidla | hi spmm2 | 14:36 |
frood66 | davidla: now would be qa god time to tell us yr thoughts | 14:36 |
spmm2 | hi DrL | 14:36 |
davidla | that was the initial structure we started with | 14:36 |
davidla | but you should feel free to change it in anyway you like | 14:36 |
spmm2 | tx | 14:37 |
frood66 | so the initial structure is of no value? | 14:37 |
beta_helix | @mottiger that is strange, I see that as well (will bring it up to the devs) | 14:38 |
davidla | auntdeen, you can have bonds to the initial structure if you like | 14:38 |
davidla | definitely try whatever you think would work best | 14:38 |
@auntdeen2 | yes - but exactly is it that you are looking for? | 14:39 |
Lazarus-uk | yes, beta, there is a feedback posted about <15 and <150 | 14:39 |
mottiger | it's another mutate GAB puzzle | 14:39 |
spmm2 | having moveable sidechains in the socket area is great | 14:39 |
@auntdeen2 | sorry - what exactly? | 14:39 |
mottiger | if the sidechains in the virus protein are flexible, don't we change the backbone then? | 14:40 |
frood66 | well i got my answer | 14:40 |
davidla | auntdeen2, we don't have any assumptions what this small 3 amino acid should look like | 14:40 |
davidla | just as long as it can fit in the flu viruses pocket, and can hold on tightly, that would be great. :) | 14:40 |
@auntdeen2 | thanks, davidla - but can you define "hold on tightly"? | 14:40 |
@MikeCassidyToo | Yes i can also play all three 546s | 14:41 |
beta_helix | @Lazarus thanks, I assigned it | 14:41 |
frood66 | so this is no different to recent puzzles? | 14:41 |
beta_helix | @Mike we'll get that fixed soon, I can manually change it but I want the devs to diagnose the issue first! | 14:41 |
davidla | mottiger and frood66: you can definitely change the backbone | 14:42 |
frood66 | so? | 14:43 |
davidla | we want you to change the backbone | 14:43 |
beta_helix | but not the backbone of the virus ;-) | 14:43 |
mottiger | nope i mean on the locked virus protein | 14:43 |
davidla | oh, you cannot change the backbone of the virus | 14:43 |
mottiger | the sidechains are moving | 14:43 |
frood66 | thankyou - some direction | 14:43 |
mottiger | but the backbone is fixed | 14:43 |
davidla | we assume that will stay the same | 14:43 |
mottiger | which is very nice i think but isn't the danger that we damage the protein too much? well wait, that's what we want | 14:44 |
beta_helix | @spmm we figured you would all enjoy having some flexible sidechains on the virus :-) | 14:44 |
frood66 | please beta | 14:45 |
Susume2 | I wish bonds to the virus could count for more points than bonds just on the ligand | 14:45 |
spmm2 | :D - roughly how big is the rest of the small piece or will that vary | 14:45 |
Psych0Active | absolutly! | 14:46 |
davidla | we are letting you change the residue orientations to help make the 3 amino acid piece fit better | 14:46 |
beta_helix | @susume that is something we could probably add in future puzzles. | 14:47 |
frood66 | so u r making it easy? | 14:47 |
davidla | spmm, so what we wan to do is take this 3 amino acid piece and transplant it on to another small protein that would be 40-250 amino acids long | 14:48 |
mottiger | what are the plans with the already produced data of foldit? do we have chance to see another round of the flu puzzle with data of us? and how will that look? | 14:48 |
beta_helix | @frood66 no, we just wanted to start by giving you more freedom before restricting you too much. In previous Flu Puzzles we started VERY constrained and then relaxed those parameters in future puzzles. We wanted to go the other way this time. That is why the constraint is very far on this puzzle. | 14:48 |
davidla | we don't know the exact protein we would like to place it on just yet, it depends on the type of solutions you guys can come up with. | 14:49 |
mottiger | do you compare our solutions with already known proteins? and then try to modify it or is it a complete new design? | 14:50 |
TimovdL | How valid is the assumption that the backbone of the virus will stay fixed when the blocker is there? | 14:50 |
frood66 | would have helped if u had said so in the first place beta - many have been here longer than I. think u owe ythem that | 14:51 |
davidla | mottiger: we would like to compare your new solutions with known solutions, yes | 14:51 |
beta_helix | @mottiger I'm getting one of the Scientists from a previous puzzle to come and answer your question :-) | 14:51 |
davidla | i'm optimistic and very excited to see all the possibilities there are | 14:52 |
frood66 | Hmmmm | 14:52 |
Susume2 | Any chance of designing a protein that mimics the bit of the human cell that the virus bnids to? | 14:53 |
mottiger | yeah i can understand that excitement but with time it is getting a bit boring just grinding with 3 segments, but i think we need to build a solid base to make a nice protein later on | 14:53 |
beta_helix | EvdH can answer that, mottiger | 14:53 |
@EvdH | Hi guys! | 14:53 |
frood66 | hi | 14:54 |
Psych0Active | Hi :) | 14:54 |
@MikeCassidyToo | hi EvdH | 14:54 |
davidla | TimovdL, from all viral structures of this virus that we know of, the backbone remain the same either bound or unbound | 14:54 |
TimovdL | tx | 14:55 |
spmm2 | HI EvdH - any early results from the earlier puzzles | 14:55 |
beta_helix | The blogpost has a great link to a diagram showing the Flu Virus: | 14:55 |
beta_helix | http://fold.it/portal/node/992416 | 14:55 |
@EvdH | Well mottiger, these 3 residues actually make up the most important part of the binding motif towards the protein. So they may look as only 3 small residues but they have a huge impact. We are going to graft these three residues onto a larger protein, so we can really create a protein-protein interaction | 14:55 |
davidla | Susume2: yes, essentially, this is the first step towards mimicking the human cell receptor | 14:56 |
Psych0Active | Wow! :) | 14:56 |
@EvdH | sure spmm2! Actually I'm currently analyzing all of the 60,000 solutions all the Foldit players came up with. | 14:56 |
@EvdH | But it's not as straightforward as only looking at the top10 highest scoring models ;) | 14:57 |
mottiger | and can we see any of these exciting binders someday? | 14:57 |
Psych0Active | How so? | 14:57 |
frood66 | no kidding | 14:57 |
@auntdeen2 | that was my earlier question... how are you defining "hold tightly"? | 14:58 |
@EvdH | That is indeed the ultimate goal mottiger :) | 14:58 |
@auntdeen2 | are backbone bonds better than sidechain bonds? | 14:58 |
mottiger | like gallery mode or so, you can load several solutions you think they are really promising, without being able to touch them, just like in a museum | 14:58 |
frood66 | aunty - nice - i want to know that | 14:59 |
beta_helix | we love the backbone bonds! | 14:59 |
beta_helix | but we don't know if there score better | 14:59 |
davidla | auntdeen2: hold tightly would be number of hbonds you can make with the 3 amino acids you select | 14:59 |
davidla | also, don't forget the pocket you are targetting is hydrophobic | 15:00 |
@auntdeen2 | we do too, lol - but are better than sidechain bonds for your purposes? | 15:00 |
davidla | so putting hydrophobic type residues in the pocket would be very nice | 15:00 |
frood66 | we await an answer | 15:00 |
infjamc | How can you prevent abuses such as poly-tryptophan, though? | 15:00 |
beta_helix | yes, because they are more likely to be there (since the Flu can mutate its sidechains a lot more easily) | 15:01 |
@auntdeen2 | I do ask simply because our software doesn't seem to value the bonds as much as it seems it should | 15:01 |
beta_helix | @infjamc we're using a newer score function that seems to be working well. | 15:01 |
frood66 | yea yea yea | 15:01 |
gdnskye | so the more the better - hbonds? | 15:01 |
infjamc | beta: does the new score function limit the effectiveness of the "four glutamates / four arginines" trick as well? | 15:02 |
davidla | gdnskye: yes | 15:02 |
gdnskye | thanks | 15:02 |
frood66 | guess we are all asking for a little guidance | 15:03 |
mottiger | hihi, we are doing science, there is no guide to it | 15:03 |
spmm2 | I quite like these small ones because they are flexible enought to just try lots of positions | 15:03 |
frood66 | that is simple mott - not what i said | 15:04 |
spmm2 | cheer up frood | 15:04 |
@mimi2 | always the arguement that if we don't know it isn't right we will be prepared to try the impossible | 15:04 |
frood66 | never so happy spmm | 15:04 |
beta_helix | @frood please restate your answer (there are a lot of questions!) | 15:04 |
frood66 | yes mimi | 15:04 |
frood66 | beta: i had no answer | 15:05 |
beta_helix | restate your question (sorry... many people talking in this room!) :-) | 15:05 |
beta_helix | @infjamc yes, that should also have been fixed. We haven't seen these issues crop up in any of the top solutions recently! | 15:07 |
frood66 | there is , perhaps, the problem - be straight - these lab rats may have a better chance | 15:07 |
beta_helix | @frood I am very sorry, but I still don't understand your question. Do you have something you want DavidLa to answer before he has to leave? | 15:08 |
frood66 | not sure i did - that must be yr imagination | 15:08 |
beta_helix | Anyone have any last questions for DavidLa before we move on to the new Symmetry Puzzles? (I will post it in Gallery Mode) | 15:08 |
@auntdeen2 | please, devs - I am still looking for the answer to your definition of "hold tight" | 15:09 |
spmm2 | DrL - can we assume that there will be extensions from both ends of the 3 a piece ? | 15:09 |
Susume2 | is there anything besides hydrogen bonds that helps the protein stikc to the virus? | 15:09 |
beta_helix | @frood, ok good! I was afraid we didn't answer your question because we read "we await an answer" | 15:09 |
frood66 | it is an old navy term | 15:09 |
aSuAhSaD | i just want to say that i enjoy this prograsmm very much but now i have to go to learn tomorrow what i do in this prog | 15:09 |
davidla | ok, hold tight means: more hydrogen bonds of the tripeptide to the virus | 15:09 |
beta_helix | @spmm I'll post the puzzle in Gallery Mode so you can try it out! | 15:10 |
davidla | also, more hydrophobic contacts | 15:10 |
@auntdeen2 | on puzzle 543 atm - I am at r18 with 4 bonds - 2 to backbone, a 5th is the small piece backbone to itself | 15:10 |
davidla | to hydrophobic type residues of the virus | 15:10 |
spmm2 | cool thanks | 15:10 |
mottiger | my current rank 8 flu2 has just two hbonds | 15:10 |
mottiger | i don't like the solution but it seems to score well | 15:10 |
@marie_s | hold tight is also : if you try to get itout, it doesnt want? | 15:10 |
@auntdeen2 | but mott on my team has a higher score with just 2 bonds to the frozen peice | 15:11 |
frood66 | hold tight mott | 15:11 |
@auntdeen2 | so I am wondering | 15:11 |
davidla | if you are doing hydrophobic packing, you don't need hbonds | 15:11 |
davidla | btw | 15:11 |
@auntdeen2 | so the bonds do not matter then? | 15:11 |
frood66 | why is this not in the puzzle notes? | 15:12 |
@MikeCassidyToo | In the AD all we can do is through the score if that is leading to the wrong place they will modify the scoring | 15:12 |
@auntdeen2 | thank you, that does answer (but really makes me wonder then what our gauge is) | 15:12 |
davidla | for hydrophobic residues, there are no side chain hbonds | 15:12 |
beta_helix | @auntdeen sadly your gauge is the score function (as you well know) | 15:12 |
frood66 | how much time would u guys like us to waste? | 15:12 |
Susume2 | beta does the hydrophobic packing show up inthe packing component of the score? | 15:13 |
@CFC | easy frood | 15:13 |
frood66 | cfc: explain? | 15:13 |
frood66 | that was a fair comment | 15:13 |
frood66 | tell me it was not | 15:14 |
davidla | one thing this is leading to is molecular mimicry | 15:14 |
davidla | the virus you are targetting now binds to a known ligand, called sialic acid | 15:14 |
davidla | one thing i have in mind the future is to put sialic acid as part of this flu puzzle, overlay it so that you can put residues int to try to mimick it | 15:15 |
Susume2 | that would be very cool | 15:15 |
beta_helix | @frood I would say: play as long as you enjoy it. Don't waste any time on Foldit once it makes you cranky :-) | 15:16 |
phat865 | Hi | 15:16 |
davidla | that would be really awesome. but for this puzzle, we wanted to see if you guys can beat sialic acid | 15:16 |
beta_helix | Ok everyone... it's time to let DavidLa get back to work! | 15:16 |
@marie_s | thanks davodla | 15:16 |
harp | Thanks David | 15:16 |
davidla | if you guys can find something that would bind more tightly than the native receptor, that would be incredible | 15:16 |
Susume2 | thank you DavidLa | 15:16 |
davidla | judging by the amino acids in this virus's pocket | 15:17 |
davidla | i really believe that there are lots of great opportunities for this | 15:17 |
gdnskye | thanks davidla | 15:17 |
mottiger | this is also work beta ;) | 15:17 |
beta_helix | I have posted DrLemming's puzzle in Gallery Mode, here is his general blogpost: | 15:17 |
beta_helix | http://fold.it/portal/node/991246 | 15:17 |
@MikeCassidyToo | TY davidla and beta_helix | 15:17 |
davidla | thanks guys! | 15:17 |
TheGUmmer | ty | 15:17 |
spmm2 | thanks i always wondered why those orange packed areas scored so well without visible clues of bonds | 15:17 |
davidla | i can't wait to see what you guys come up with | 15:18 |
beta_helix | @mott with you guys doing the hard work! :-) | 15:18 |
DrLemming | Hey everyone! DrLemming here. New puzzle to check out in gallery mode! It's a mostly-free-form symmetry/design puzzle. Let me know if you have questions! | 15:18 |
TheGUmmer | drat missed it | 15:19 |
mottiger | well it isn't really work beta, you can not make any thoughts about what should i put there, my point is just let your mutate script run and hope for the best | 15:19 |
mottiger | it is a dimer, not a trimer | 15:19 |
DrLemming | Ah, does the description say trimer? Whoops. Let me check it out... | 15:19 |
mottiger | i have trimer in mind | 15:20 |
beta_helix | @TheGUmmer you still get the second half of the Scientist Chat :-) | 15:20 |
DrLemming | Ah, gotcha. That's an old blog post for a related puzzle. | 15:20 |
mottiger | ah okay | 15:20 |
DrLemming | But it's the exact same idea: taking an existing trimer or dimer and expanding it so we can do more with it. | 15:20 |
TheGUmmer | o | 15:20 |
mottiger | and what do you plan to do with it? | 15:21 |
DrLemming | Okay folks, I might post a long-form puzzle description here. Large text block incoming! | 15:21 |
DrLemming | Structured dimeric and trimeric peptides are great starting points for a major bioengineering challenge. Specifically, they can be used as building blocks for designing useful, rigid assemblies of proteins, like crystals and nanocages. The smallest such starting point for this kind of design is an ...WXCXW... motif, which forms a tiny structured homodimer: | 15:21 |
beta_helix | @TheGUmmer (and anyone just joining): check out the new puzzle in Gallery Mode and ask DrLemming any questions you have about it! | 15:21 |
DrLemming | a short beta sheet stabilized by a cross-strand disulfide bond and two tryptophan/tryptophan interactions. The only problem: this motif is so tiny, it is difficult to do anything with; it needs to be larger but retain rigidity. Otherwise anything goes: beta sheets, alpha helix docking, rigid loops, you name it. We've given you 20 extra residues to play with | 15:21 |
DrLemming | @mottiger: I'm trying to assemble small dimers and trimers into nanocages, rigid crystals, and other interesting scaffolds. Basically, I'm trying to make a really useful lego piece. :) | 15:22 |
DrLemming | So it could be used for a number of things. | 15:22 |
silverberg | Is it bad that I have no idea what you are talking about, and that is not an insult. I just play the game. | 15:22 |
silverberg | Like these extra residues. What do I do with them? | 15:23 |
mottiger | name it please, why are we interested in nanocages, maybe drug delivery? | 15:23 |
beta_helix | @silverberg don't worry... you just joined us in the middle of a Scientist Chat. No more big blocks of text, we promise! :-P | 15:23 |
silverberg | I was here at the beginning. | 15:24 |
frood66 | thx lemming - at least u tell us what u r aiming for | 15:24 |
TheGUmmer | take notes, there will be a quiz later | 15:24 |
frood66 | haha | 15:24 |
silverberg | I read what you type, but I do not have the understanding (yet) to er.. understand. | 15:24 |
@auntdeen2 | (I know I will fail :-P ) | 15:24 |
DrLemming | @mottiger: drug delivery is one interesting application, but something I'm really excited about is using nanocages to template metal nanoparticle assembly. | 15:24 |
frood66 | aunty - that is not the attitude | 15:25 |
@auntdeen2 | ;-) | 15:25 |
DrLemming | But, in a general sense, I just want you all to design some dimers that look really cool. That's the... secondary objective. :) | 15:25 |
beta_helix | @silverberg for the Flu puzzle, there is a cool diagram if you click on the link in the blog: | 15:25 |
beta_helix | http://fold.it/portal/node/992416 | 15:25 |
DrLemming | In terms of design: just have fun! Anything low-energy. But please try to preserve the orientation of the frozen residues. (It's possible to break them apart, even though they're frozen.) | 15:26 |
silverberg | thanks. But no worries, it is a learning curve for me, and I like a challenge. | 15:26 |
spmm2 | metal naoparticles - is that similar to the work being done using gold to identify target areas | 15:26 |
beta_helix | @silverberg that's what I love to hear! | 15:27 |
mottiger | so if you really interested in these cages, can you somehow force us to do something in that direction? | 15:27 |
silverberg | Yay! | 15:27 |
frood66 | DrL - thx - nice to have direction | 15:27 |
DrLemming | @spmm2: sort-of. That's a really good biological application of metal nanoparticles, but I'm just interested in being able to make nanoparticles of a very specific size; not thinking so far ahead that I'm considering new applications. | 15:28 |
@marie_s | the 2 frozen part have to stay where they are ? | 15:28 |
spmm2 | tx | 15:29 |
DrLemming | @frood66: I can provide specific suggestions if you'd like. A large beta sheet should probably work (making a hairpin using the central strand as one of the sheets). | 15:29 |
DrLemming | @frood66: it's something to try, anyway, if you're after specifics. | 15:29 |
DrLemming | But in general, I want this to stay very free-form. | 15:30 |
frood66 | DrL: well it mght help - thx | 15:30 |
DrLemming | @marie_s: great question! Yes, the frozen stuff should stay in place. However, some of the frozen residues can be mutated. | 15:30 |
@marie_s | they are not frozen one near the other | 15:31 |
TheGUmmer | IMAGE: http://fold.it/portal/files/chatimg/irc_12518_1334874694.png | 15:31 |
spmm2 | oh wow a mutating dimer - hours of fun :D | 15:31 |
DrLemming | @marie_s: It's possible to pull the central beta sheet apart, but this will probably result in very poor energies.... | 15:31 |
@marie_s | ok we have to try not to explose the pair | 15:32 |
beta_helix | @spmm that's what we thought as well! | 15:32 |
TheGUmmer | everyy other seg on the sheets has its structure locked | 15:32 |
DrLemming | OH, the secondary structure assignment isn't frozen; gotcha. Feel free to change the designation to loop if you'd like; it could help mark which residues are fully frozen, and which have sidechains that can be mutated. | 15:33 |
mottiger | may it is usefull in a first stage to completly freeze these two sheets | 15:34 |
DrLemming | @TheGUmmer: correct. All segments that face "up" are locked (two tryptophans and a cysteine on each strand) , while "down" is not sidechain-locked. | 15:34 |
frood66 | DrL: so sneaky | 15:34 |
@marie_s | they are not, we can split the pair | 15:34 |
DrLemming | @mottiger: technically the backbone is frozen for all 5 residues, but unfortunately we haven't been able to add cross-interface constraints to keep those 5 frozen residues in perfect alignment with each other. | 15:35 |
frood66 | i am looking for a bigger machine | 15:35 |
@marie_s | ah ok | 15:35 |
DrLemming | @mottiger: we're working on a fix, but we may have to launch the puzzle as-is. Hopefully not a major issue; when the frozen strands are pulled apart, it shouldn't score as well. | 15:36 |
mottiger | you never know what we are able to create | 15:36 |
frood66 | oh boy | 15:36 |
DrLemming | @mottiger: indeed! :) Looking for some creative, low-energy designs. | 15:37 |
beta_helix | Are there any other questions for DrLemming? | 15:37 |
DrLemming | Design note: One side of the beta sheet has residues that can be mutated, so that players have the option of packing it against another chain. | 15:38 |
DrLemming | Oh, I should mention: I will actually be making at least one of these designs. | 15:38 |
DrLemming | One of the lowest energy designs. (Maybe not the very lowest, in case there's still an exploit we missed.) | 15:39 |
frood66 | terifican exploit? | 15:39 |
spmm2 | is it possible to have the shadow of the moveable piece a different colour to the frozen piece | 15:39 |
mottiger | what do you mean with making? synthesis? | 15:39 |
frood66 | eek - exploit? | 15:39 |
DrLemming | @mottiger: yes! Chemical synthesis (since it's so short) and then an NMR or X-ray structure, if it folds well. I might make more than one. | 15:40 |
DrLemming | And I'll let any players/designers know how it turns out, if I use theirs. :) | 15:40 |
mottiger | i always wanted a nmr of an own designed protein | 15:41 |
frood66 | fantastic | 15:41 |
alwen | lol, mott | 15:41 |
spmm2 | so for the dimer - there is no 'native''? | 15:41 |
frood66 | hey spmm | 15:41 |
DrLemming | @spmm2: good question; I'd have to ask the devs. That would be convenient! | 15:41 |
DrLemming | @spmm2: there is sort-of a native. Essentially, the frozen residues are taken from the native NMR structure. However, it's not in the PDB. | 15:42 |
DrLemming | @Just seven amino acids (XWXCXWX, where X can be anything) folds up into a very stable beta-sheet dimer. I'd like to see how we can add to that dimer. :) | 15:43 |
spmm2 | tx - q was really more of çloser to the native' vs top score | 15:43 |
DrLemming | (sry; @spmm2 for above post.) | 15:43 |
@thomirc8 | Is there an energy value (i.e. Foldit score) for the native that can be posted? | 15:44 |
@thomirc8 | either will do - we can convert ;-) | 15:44 |
frood66 | o golly | 15:45 |
DrLemming | @thomirc8: Ah, I see. The starting structure is effectively the native structure; the frozen residues are already optimized. So I don't really have an energy for you, other than what the puzzle starts with. Sry. | 15:45 |
@thomirc8 | no, that works - thanks | 15:45 |
@thomirc8 | and for the record beta (it came up last night), all puzzles are now scoring disulfide bonds, right? | 15:46 |
mottiger | so what are you doing now? waiting until we produce a nice solution and make coffee for the postdocs or have you other projects, may related to this onee? | 15:46 |
frood66 | steady mott | 15:47 |
DrLemming | @mottiger: PLENTY of other projects. :) (Spread between 3 labs!) Though making myself coffee does sound good. ;) | 15:47 |
beta_helix | @thom yep... disulfides should be all good from now on! | 15:48 |
@thomirc8 | thank you | 15:48 |
DrLemming | @mottiger: also, I'll be doing a re-run of this puzzle using an N-terminal extension instead of the current C-terminal extension. (Same 20 residue extended chain to play with, but on the opposite side.) | 15:48 |
DrLemming | @mottiger: But I'll see how it goes first. (There may be more issues to address, etc.) | 15:48 |
mottiger | so you are playing yourself? | 15:49 |
frood66 | r u being me mot? | 15:49 |
mottiger | i'm just curious about what is behind the scene | 15:49 |
beta_helix | Five more minutes left in the Scientist Chat everybody... | 15:49 |
DrLemming | @mottiger: yep. I use Foldit for design regularly; it's really handy. :) | 15:50 |
beta_helix | most of the people in David's Lab working on design use Foldit on a daily basis! | 15:50 |
frood66 | mott: yes - been there - drop it - message me? | 15:50 |
mottiger | handfolding or also using scripts? | 15:50 |
spmm2 | I wanted to ask about how the scientists visualised proteins and interactions or if they did at all | 15:50 |
DrLemming | @mottiger: I have a few related designs that I like, but I want to wait until I get the results back before I synthesize or order peptides, because chances are a regular Foldit player will come up with something better! :D | 15:50 |
mottiger | then wouldn't be interesting let us work on already existing solutions? | 15:51 |
spmm2 | also as you have already answered that question - with the results anyalysis - what tools do you use to crunch the numbers | 15:52 |
spmm2 | and then visualise the results? | 15:52 |
@thomirc8 | it would also be be neat to see how you all use foldit vs. how we do it (such as view options) | 15:52 |
mottiger | minimal view options to have as much clients as possible ;) | 15:53 |
frood66 | mott: stop it | 15:53 |
beta_helix | @spmm EvdH can tell you how he analyzed Puzzle 539: | 15:53 |
beta_helix | http://fold.it/portal/node/992285 | 15:53 |
DrLemming | @mottiger: I don't have any solutions that I feel good enough about to share right now; would prefer not to taint the imaginations of the players. :) | 15:53 |
mottiger | please drlemming, don't be ashamed ;) | 15:53 |
DrLemming | @mottiger: It's been tricky to design something that looked good, which is part of the reason that I chose this as a design puzzle. Very excited to see what players come up with! | 15:54 |
@thomirc8 | beta: would it make sense to have these gallery puzzles open to uploads? | 15:54 |
frood66 | mott | 15:54 |
mottiger | vote for permanent gallery view for puzzles where people can contribute their solutions if they want | 15:54 |
beta_helix | I think that's a great idea! | 15:55 |
@EvdH | @spmm2 for the Immuno design puzzle we first make use of filters which are based on some thresholds. For example, I first look which kinds of unique solutions exist, and I then select the top one. Next step is to calculate (in this particular case) the binding energy of the 3 residues with the big protein, so this gives a measure how tight the binding would be. | 15:55 |
DrLemming | @thomirc8: My fav. settings are: show all bonds, but not exposeds or voids by default, until I'm double-checking packing. I alternate between cartoon and all-atom stick, etc. | 15:55 |
beta_helix | @mottiger In fact, EvdH and I were just talking about posting some of his favorite 539 solutions into gallery mode | 15:55 |
mottiger | help me, what is 539 | 15:56 |
mottiger | was | 15:56 |
beta_helix | http://fold.it/portal/node/992285 | 15:56 |
spmm2 | being able to intereact with top solutions would be great much better than pictures | 15:56 |
@EvdH | Yep, I think it would be nice to give you guys a nice sneak preview of some cool solutions :) | 15:56 |
DrLemming | @thomirc8: but I think most folks in the Baker Lab have different fav. settings; depends on personal preference. I deal mostly with very small stuff, so I like to see as much info as possible; very cumbersome for larger proteins. | 15:56 |
beta_helix | @spmm of course! | 15:56 |
mottiger | a lot of people would be super interested in this | 15:56 |
tokens | Will the solutions we are making in the gallery puzzle now be saved and usable for when the puzzle comes up for real? | 15:57 |
mottiger | pictures in the wiki are nice, but looking into a protein deep and compare them can be fun too | 15:57 |
tokens | So the current work is not wasted | 15:57 |
frood66 | EvdH: enough now | 15:57 |
beta_helix | Any last questions for DrLemming? | 15:57 |
harp | that would be very interesting | 15:57 |
frood66 | beta: square this mess off | 15:58 |
frood66 | now would be good | 15:58 |
mottiger | when will the puzzle be posted? | 15:58 |
beta_helix | @frood66 I don't understand your comments... nobody is forcing you to take part of this chat. You can uncheck the Global Chat box if you are unhappy. | 15:59 |
beta_helix | @mott Probably early next week. | 15:59 |
DrLemming | @mottiger: very good question. I... am not 100% sure. Oh, nm, answered. :) | 15:59 |
frood66 | look back beta | 15:59 |
DrLemming | @mottiger: We will try to constrain the two frozen sections so they can't be yanked apart and destroyed... but no guarantees. :( | 15:59 |
mottiger | even if you can fix it, i'm sure someone will find a way to destroy it anyway *lol* | 16:00 |
DrLemming | @mottiger (symmetry is still in its infancy. There are some occasional... side-features... to address.) | 16:00 |
spmm2 | thanks for coming and answering questions - changing the colour of the shadow pieces would help me a t least | 16:00 |
beta_helix | @frood I am looking back and only seeing negative and rude comments from you, feel free to PM me if you want to discuss this further. | 16:00 |
@marie_s | I think we can try like this | 16:00 |
spmm2 | yes agree marie | 16:00 |
DrLemming | @mottiger: indeed! Foldit players are incredibly creative like that. ;) But I'd at least like to make it less fragile, if possible. We'll see. | 16:01 |
beta_helix | @spmm I'll bring that up at the Foldit meeting tomorrow | 16:01 |
silverberg | yes, thanks beta | 16:01 |
beta_helix | @marie great, that's why we wanted to double-check with all of you in gallery mode during the chat (so you could tell us if anything was wrong or confusing!) | 16:01 |
beta_helix | Ok gang, please thank EvdH and DrLemming for stopping by! | 16:01 |
DrLemming | @spmm&beta_helix Yeah! Should be a fairly simple fix: color change of shadow-symmetry partner vs. frozen. | 16:01 |
@marie_s | thnaks all | 16:02 |
mottiger | come back soon evdh and lemming | 16:02 |
@auntdeen2 | thanks, all :-) | 16:02 |
@mimi2 | thanks all very interesting | 16:02 |
silverberg | thank you EvdH and DrLemming | 16:02 |
spmm2 | beta before you dash off | 16:02 |
DrLemming | Thanks everyone! I'll try to address any more questions as they come up, once we post the puzzle! :) | 16:02 |
beta_helix | Thank you all for your hard work! | 16:02 |
harp | Thanks exciting stuff | 16:02 |
frood66 | thx | 16:02 |
DrLemming | Happy designing! | 16:02 |
gdnskye | yes thanks evdH and doc - was a great chat | 16:02 |
@EvdH | no problem, was interesting again :) | 16:02 |
mottiger | and i hope we can provide you some nice results, but please keep us informed what you are doing and present some of the intersting stuff | 16:02 |
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