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!
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….)
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?
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.
Have there been enough results from the design puzzles using the Blueprint tool to draw any conclusions?<p>
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?<p>
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.<p>
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) … ?
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
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.
I would like to assess my own sequences. What is the protocol for that?
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!
