Developer Chat

--- Log opened Fri Jun 08 11:36:39 2012
BletchleyParkirc thanks cfc 11:36
beta_helix @BP mostly because we are giving you 4 CASP puzzles at the same time! 11:37
BletchleyParkirc ok, thanks :) 11:37
beta_helix We don't expect you to spend an entire week on this puzzle, but want to make sure everyone has enough time to work on it (with all the CASP puzzles, and the Euros... ;-)) 11:37
EvdH_ Furthermore in the previous design puzzles we noticed that there are still useful solutions created after 7 days :) 11:37
beta_helix also, David Baker wants to post Flu and Symmetry puzzles as well! 11:38
BletchleyParkirc very good, this week ? 11:38
beta_helix Probably next week, once we get all the Category bugs sorted out! 11:39
Marktoo it is nice to work on something a little different sometimes 11:39
@mimi2 any particular sidechains that you would expect / prefer to be present on the helix? 11:40
EvdH_ mimi2: thats a good one 11:40
EvdH_ mimi2: as you have noticed the Fz domains contains a quite hydrophobic cavity 11:40
EvdH_ so it would make sense to dock something hydrophobic in there (ie phe's or ile's) 11:41
EvdH_ furthermore the crystal structure which was solved of this Fz protein contains a very hydrophobic molecule in that cavity. So this is a second hint for us to use hydrophobic side chains 11:42
beta_helix @Marktoo yes... of course, we get very sick of the CASP puzzles as well! (At least there will be a bit of variation coming up as this week they released a bunch of Refinement puzzles) 11:42
TimovdL And on the other side hydrophilic? 11:42
EvdH_ TimovdL: yes, those will give you a nice score. But since they don't make any contacts with the Fz domain they are not very important 11:43
@mimi2 there doesn't seem to be much opportunity for bonding - but I've only taken a brief look 11:45
EvdH_ mimi2: this is indeed about the hydrogen bonding vs the hydrophobic interactions 11:46
EvdH_ in this puzzle there is indeed not much room for hydrogen bonds, but there is a lot of room for hydrophobic interactions (even though they are not yet visualized in Foldit) 11:47
TimovdL Any news on that? 11:47
beta_helix tamirh is working hard on implementing Hydrophobic Interactions in a nice Visual way: 11:47
beta_helix 11:47
*** mode/#global [+o Rav3nIRC] by ChanServ 11:47
chantzt Let's have a little Wnt intro: The work that discovered it happened about 30 years ago 11:50
chantzt Since then, many groups have tried to get structures for it, but the hydrophobic parts that bind where you are trying to bind with the helix make this difficult 11:51
@rav3n_pl hello folders 11:52
@rav3n_pl did I miss chat? 11:52
@mimi2 ongoing rav 11:52
chantzt As of last week, one group published the first results that show how Wnt binds to Fz 11:52
Dhalion :waves: 11:52
@rav3n_pl (oops) 11:52
beta_helix No, you are right in the middle of it 11:52
beta_helix :-) 11:52
chantzt We want to quickly find a way to bind to Wnt's target, because it is one of the most crucial developmental proteins that scientists are studying at this time 11:54
beta_helix Feel free to ask EvdH or chantzt any questions about the new Design Puzzle, Rav3n_pl... 11:55
chantzt Wnt signaling errors are found in a number of cancers and it also plays a vital role in normal tissue development during life 11:55
TimovdL Is there no insight of the structure that wnt has in the binding region? 11:55
bobcat What are 'signaling errors'? 11:55
EvdH_ TimovdL: Yeah there is, it a long lipid structure (not a 'normal' compound of a protein) so we are now trying to mimic that, by using the hydrophilic side chains on the helix 11:58
chantzt bobcat: The Wnt signaling 'errors' are usually related to signaling too strongly through Fz or Wnt's other receptors (i.e., there may be too much Wnt present) 11:58
blobfolder can i deform the helix? 11:59
@rav3n_pl *lurking at design puzzle* 11:59
TimovdL So we are trying to build a protein that does a lipid job 11:59
EvdH_ yes you can, but by totally deforming a helix it will be difficult for us to use. So we will mostly pay attention to helical solutions 12:00
@rav3n_pl hmm why that little thing is not pulling in when wiggle on low ci? 12:01
BletchleyParkirc there are constraints in the puzzle rav 12:01
chantzt TimovdL: That is exactly what we are aiming for! We want to use our protein engineering techniques to reliably replace this very strange lipid binder. 12:01
@rav3n_pl ok, i ned clash it to make it fly :P 12:01
TimovdL That should be reflected in the scoring function, else you wil get not so much 12:02
@rav3n_pl "Tissue regeneration" ? Cool :) 12:02
@rav3n_pl patch/bandage from Star Trek :D 12:03
chantzt rav3n_pl: Yep! It reflects some scientist's hope that we can use Wnt to guide/reprogram cell development 12:03
EvdH_ Well TimovdL the solutions so far mostly contain only helices, so I think we are heading the right direction :) 12:03
@rav3n_pl lol i made 310 helix on it :P 12:05
@rav3npl IMAGE: 12:05
@rav3n_pl maybe this IS soluton :D 12:06
EvdH_ Looks interesting :) 12:06
BletchleyParkirc Is the score function a reliable guide for the solutions in this puzzle ? 12:06
EvdH_ BletchleyParkirc: that is a good point indeed. When we are analyzing your results we also use other metrics than the  score Foldit gives us (ie, how much area is buried, how well to the proteins mach each other curvature etc) 12:08
beta_helix *match each other 12:08
BletchleyParkirc okay, thanks. 12:09
Susume2 foldit score reflects hydrophobic interactions, right?  it's only yhe visualization of them that's not been added yet? 12:09
@rav3npl IMAGE: 12:09
beta_helix @Susume exactly :-) 12:09
@rav3n_pl (end of spam) 12:09
@rav3n_pl so we will have phobic visualisations too? 12:10
EvdH_ Susume2: your totally right :) 12:10
beta_helix @rav, hopefully soon: 12:10
beta_helix 12:10
beta_helix tamirh is actually showing us his latest visualization tests later today at our weekly Foldit meeting. 12:11
Brow42Irc Does this table "Hydropathy Compatibility Index" affect foldit scoring: 12:11
@rav3n_pl looks like Tamir is getting more and more work on shoulders :) 12:11
beta_helix @rav Yes, we are very happy to have him on board! 12:12
EvdH_ Brow42Irc: This hyrophobic effect is indeed covered by the current scoring function of Rosetta/Foldit. It only doesn't make use of exactly this protocol 12:14
beta_helix Any last questions for chantzt and EvdH? 12:14
blobfolder could rules like "keep it a helix " be part of the bonusses and conditions system? 12:14
@rav3n_pl i remember puzzle like that... part need to be a helix to score count 12:14
BletchleyParkirc something can have the property of a helix, yet not look like one. I think in this case it is important it also looks like one. 12:15
EvdH_ We are not sure what solutions will be the best, so that is the reason why we will repost this puzzle somewhere in the future, but then with the small peptide as a sheet instead of a helix 12:16
EvdH_ further more we didnt want to restrict you too much by enforcing a perfect helix, a small degree of deformation of the helix might yield some very interesting results 12:16
blobfolder good to know, thx 12:17
beta_helix Any last questions? If not, let's thank chantzt and EvdH for this Scientist Chat! 12:17
@mimi2 thanks to them and you too 12:18
BletchleyParkirc thank you ! 12:18
Lazarus-uk thanks, chantzt, EvdH 12:18
@marie_s thanks 12:18
beta_helix And we'll make sure not to schedule future Scientist Chats during the Euro games :-) 12:18
TimovdL tx 12:18
@CFC Russia 2-0 ? job done, i think 12:19
EvdH_ Thanks for the input everyone :) 12:19
chantzt Thank you for your questions and for all of your Foldit contributions! 12:19
frood66 thx guys - i'm rethinking now :) 12:19
TimovdL Beta, will the new visualisation be tested by a RG colorblind? Or a filter that simulates it? 12:20
beta_helix @timovdL we will make sure to let you all check out the new visualizations before we add them to the game 12:21
TimovdL suggestion, make the hydro bonds blue and the phobic orange 12:22
@rav3n_pl and change that blue in selection when you playing in colors... 12:22
TimovdL second that 12:23
beta_helix I'll pass that on to tamirh, we already passed on Boots' request: 12:23
blobfolder make the colors totaly customizable :) 12:23
BletchleyParkirc can the move axis purple be a bit more flashy in color too ? 12:23
BletchleyParkirc it is hard to see on a black background 12:23
beta_helix 12:23
TimovdL There are filters that can help to see what RG can see 12:24
beta_helix Ok gang, thank you all for coming! If you have any additional questions about this puzzle, please post them in the blog and they will be answered: 12:24
beta_helix 12:24
BletchleyParkirc thank you beta 12:25
Lazarus-uk thanks, beta 12:25
TimovdL tx 12:25
* CFC problem is your end BP, but it's not clear from here what it is. I'll keep clearing bans while you sort it out 12:26
BletchleyParkirc I'll reset my chat client, thanks cfc 12:27
BletchleyParkirc off global.. bye 12:27
beta_helix bye everybody! 12:28
Dhalion bye ty 12:29

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