January Science Chat

Hi everybody! A quick announcement today- our next Science Chat is January 19. Be sure your questions get posted here (this thread, right here) so I can send them to the team in advance of the chat. As long time chat fans are aware, the more questions we have prepared ahead of time the more questions we can likely get in.

The Date: 19 January 2017
The location: #veteran, IRC
The Time: 2000-2100 (or so, but the official chat ends after an hour) GMT (aka 1200-1300 PT)
The Time Zone Converter: Right this way!

We look forward to discussing science with you!

(Tue, 01/03/2017 - 22:22  |  21 comments)
LociOiling's picture
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remix and rebuild

The descriptions of remix and rebuild in jflat06's blog post raise some questions about how things work.

First, if rebuild always works with a fragment length of 3, what does a rebuild of length 2 do? (A certain recipe defaults to starting with length 2.)

Second, it sounds as if rebuild picks its fragments based on amino acid sequence, while remix picks fragments based on shape alone. Is this correct?

Third, do either remix or rebuild pay any attention to the current secondary structure? (I'm guessing no, although a shape-based remix would in effect consider the secondary structure as shown by the auto structures tool.)

Fourth, any thoughts on the reverse remix suggested by brow42?

Fifth, does remix always return the same set of results for a given selection and a given pose? In contrast, does rebuild return a random list of results?

Sixth, when attempting to clear a non-ideal loop, remix suggestions often wipe out existing ideal loops. So the ideal loop penalty might go from -100 to -300. It's a little hard to understand why this happens, since the other loops shouldn't have moved. Is there an explanation for these somewhat non-local effects?

I like the new GUI remix interface, and wish rebuild worked the same way. (You do have to make sure the remix selection is not too near the bottom of the screen, however.) In addition to reverse remix, it might be nice to have a hybrid remix-rebuild that considers both shape and sequence. (I could imagine sliders for fine-tuning these parameters...plus a Lua interface...dare to dream....)

bertro's picture
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I would like to add in

I would like to add in regards to the Remix tool that I have never been able to find a Remix replacement when an end segment is included in the selection. It may be just me but I would like to have an explanation for this. And if a solution is not possible with Remix, what is proposed to enable us to script rebuild-like moves to end segments (other than with bands)?

jeff101's picture
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Groups: Go Science
TB and MD challenges:

Any news about the TB and MD challenges
(Puzzles 1258, 1261, 1291, 1293b, 1311, & 1312)?
Will there be sequels to these anytime soon?
Will we be able to use results from the
original puzzles in the sequels?

jeff101's picture
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Can Foldit help cure Cree Leukoencephalopathy?

See the Forum post https://fold.it/portal/node/2003247
for more details. Related to this is the status of
Foldit's drug-design tools.

gitwut's picture
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Blueprint Tool

Have there been enough results from the design puzzles using the Blueprint tool to draw any conclusions?

It has been pointed out that removing Blueprint tool constraints towards the end allows for substantial score improvement. Why is this, as it seems counterintuitive?

Although the Blueprint tool is useful for creating initial designs, developing a high scoring final result is extremely clumsy without the ability to rebuild helices. It is particularly unfriendly to the core filter, and trying to gain core usually ends up breaking one or more of the ideal loops. Remix is about the only tool left that can be used but it is rarely successful at that point.

Joined: 09/24/2012
Groups: Go Science
Natural folding process

Is there any pathway for natural folding ?

================

(example answers to clarify the question)

a) From seg 1 to seg end?

b) Or is the protein synthetized by RNA then released unfolded to water where it folds automatically in all dimensions without path?

b1) first helices and sheets then the full 3D?

c) first some strong interactions (backbone, disulfide bridges and bonds) then sidechains?

d) ... ?

Joined: 04/28/2015
Groups: Go Science
make a selection and moving a

make a selection and moving a few atoms rama map!
It is not very convenient to move one

I want to move a group of atoms. and sort them

georg137's picture
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Some basic foldit questions

It is telling that many excellent players in the foldit user community have minimal background in chemistry or biochemical science. The game could be called "Loopy Loops" with no reference to proteins at all, and it would still be just as intriguing. But that's more a Searle-ian philosophical question. My questions relate to the design and performance of the game:

1) How closely do the models parallel actual protein dynamics? How many proteins developed by users have been formulated?
2) Given the hyper-astronomical number of intermediate folding stages and final states, even if all the people on the planet were foldit players, there would be little probability of anyone achieving strong solutions. Are selected foldit puzzles presented to users in advanced, near final states?
3) Are thermal perturbations incorporated into the design of the game? Perhaps by wiggle power or clashing importance?
4) Foldit has been holding steady with a relatively constant number of core players for several years. Are there plans to dramatically grow the core? Perhaps through promotions, usability improvements or instructional videos to thoroughly explain existing features to new players?
5) Is there a plan to improve use-case testing to drive down the crash rate?

Kudos to all involved in presenting this amazing system to us.

Joined: 04/24/2014
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> 4) Foldit has been holding

> 4) Foldit has been holding steady with a relatively constant number of core players for several years. Are there plans to dramatically grow the core? Perhaps through promotions, usability improvements or instructional videos to thoroughly explain existing features to new players?
Oo! I can totally take #4 here, as it relates to marketing and not Foldit based science. :)

Turns out, we have a wealth of information available - including community made videos (most well known as the "Black Belt" series and recently the "Community Learning Exchange") and consistent introduction of new tools. In the last year alone, we introduced three major tools designed to improve our scientific results: the Blueprint panel, Remix, and of course, the Rama map.

That being said, we definitely welcome feedback and discussion (on the forums, let's not get too far from the science here!) on how to improve ways for these great materials to be more easily discovered.

Great questions and feedback!

Ebbole's picture
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Unknown proteins

I would like to assess my own sequences. What is the protocol for that?

spvincent's picture
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recent denovo proteins

FoldIt seems to have got stuck in a bit of a cycle recently. The top scoring monomer design puzzles (usually a linear-looking structure with 2 helices and 3 sheets) get recycled back as de novo puzzles: I've also seen these structures in Rosetta@home. These structures are clearly interesting but it would be good to know why.

bertro's picture
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Could someone comment on the

Could someone comment on the internal code:

LocalWiggleSequence in GUI versus structure.LocalWiggleSelected() in LUA:
Are they the same internally?
Or what would be the equivalent LUA function for this GUI one?

Extract from chat on 2017-01-13:
22:09 Wbertro TomTaylor5: converted "Wiggle by sheets" to LUA
22:09 TomTaylor5 Great
22:10 Wbertro but the code does not give the same results as the GUI one
22:10 Wbertro however it does not crash the client at the end
22:11 TomTaylor5 What would you like to hear first? The good news or the bad news?
22:11 Wbertro I think the GUI LocalWiggleSequence code is NOT the same as the LUA LocalWiggle code
22:11 TomTaylor5 That was probably the function I couldn't find.
22:12 Wbertro but the 1322 puzzle I tested them against is so sensitive that two runs don't give the same result twice
22:12 Wbertro I don't think it is a missing function
22:13 Wbertro it is simply DIFFERENT internal code, it seems
22:13 Wbertro I think I will ask on the next chat

Virgo's picture
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Previously unanswered chat

Previously unanswered chat questions:

http://fold.it/portal/node/2002443#comment-32490

Apparently, these questions have been asked at least a few times before, but have either never had any clear answers from the Foldit devs, or need to be revisited.

Q1: Will a parallel programming language, such as CUDA or OpenCL, ever be used to optimise processing speed in Foldit?

Q2: Will Foldit ever be open source?
Currently, only Rosetta is open source, not Foldit.

https://developer.nvidia.com/cuda-zone
https://www.khronos.org/opencl/

Previous parallel programming discussions:
https://fold.it/portal/node/988293
https://fold.it/portal/node/991445
https://fold.it/portal/node/992230
https://fold.it/portal/node/1998564
https://fold.it/portal/node/1998734#comment-29310
https://fold.it/portal/node/1998822
https://fold.it/portal/node/1998865#comment-29346

Previous open source discussions:
https://fold.it/portal/node/164128
https://fold.it/portal/node/986241
http://fold.it/portal/node/986352
https://fold.it/portal/node/99390

Susume's picture
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stacked aromatics, pi stacking

When ring sidechains are near each other, does the scoring algorithm reward them just being close together, or does it distinguish between good stacks and bad stacks? I know they aren't always face-to-face in nature; sometimes they are perpendicular, or parallel but offset. But the foldit score seems to reward proximity even when their angle relative to each other seems pretty much random, or one is bent away from the other.

Susume's picture
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Try different sequences on promising backbones?

When you have a foldit design that looks promising, but Rosetta doesn't settle on a single fold, do you try different sequences on that backbone to see if one of them gives better Rosetta results? Lin & Koga et al designed their backbones first and then used Rosetta to figure out what sequence would make that backbone work. Seems like the same could be done with promising foldit designs. We players are running a very small number of clients, so we can only pursue one or two or three promising sequences - using Rosetta@home would make it possible for you to test many more sequences on a given backbone.

Sometimes foldit picks an unlikely AA (like a serine in the interior just because it is crowded there) that might make the fold fail in Rosetta and in real life, but if that AA could be fixed then the fold might work.

Susume's picture
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Missing building blocks?

In figure S7 of the Lin & Koga 2015 ideal design paper (supporting information), they show which ideal loop combinations Rosetta liked best. For helix-sheet loops, BAAB (blue-red-red-blue) worked more often than GB (green-blue) or GBA (green-blue-red), but we do not have BAAB in our building blocks. For sheet-helix loops, BAB (blue-red-blue) competed well with GBB (green-blue-blue), but we do not have BAB. Would you consider adding the missing loops to the building blocks?

spvincent's picture
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I'd like to see more choice

I'd like to see more choice of ideal loops on the Blueprint panel also. In particular, there doesn't seem anything for the common Shee t- Loop (length 3) - Sheet structure.

alcor29's picture
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Blue Print and remix databases

Is there a plan to expand the Blue Print and remix databases?

frood66's picture
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This question is one I would

This question is one I would have posted. Perhaps I may go further...

I can understand the logic for these tools/filters....seems sensible to me. But I also believe the existing databases
to be small at this time (since the concepts are effectively in a testing phase perhaps)

But here's my question....

At the moment it feels as tho the libraries are small for both the reason above - and Lab preference.

Should these tools continue (and I hope they do) will the libraries have an emphasis on what the lab would like
to see - rather than what real life exhibits? Or will they be more fully populated without heavy, directional intervention
on the part of FC?

Joined: 06/06/2013
Groups: Gargleblasters
help me make better proteins....

I finally got a version of two hot dogs surfing past all filters. I shared my first version with the scientists as I once again "passed" the filter even with two backbone problems. It is the one with the score below 4000.
I know Gitwut also shared some funky examples, and I have shared one with one backbone problem before. Bottom line, I don't know that we have a big enough library or the tools to work with these puzzles and produce what you want. For example, maybe we need to rebuild two loops at the same time to get things fixed.... maybe "ideal" needs a bigger library and some tests
Direction would be helpful. A Koga style fold will not fix to ideal unless I figure out how to rework two loops at the same time -- and I have no idea now to get Blueprint to do such a layout so I am still hand folding to start. We are headed the right way - we just need more feedback and help
One suggestion -- perhaps we can get a share with programming track in addition to share with scientists. That might help us separate process from content. But I'd still like help with both
Skippy

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Will there ever be any new

Will there ever be any new H-bond network puzzles?

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