Thu, 04/19/2012

@betahelix	Hi everyone! We'll be starting the Double Scientist Chat in ~half an hour!	14:05
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