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 | http://fold.it/portal/node/992449 | 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: http://fold.it/portal/files/chatimg/irc_174969_1339182353.png | 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: http://fold.it/portal/files/chatimg/irc_174969_1339182557.png | 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 | http://fold.it/portal/node/992449 | 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: http://fold.it/portal/recipe/28691 | 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 | http://fold.it/portal/node/992449#comment-16969 | 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 | http://fold.it/portal/node/992888 | 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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