How to detect and fix backbone issues from within a Foldit LUA recipe?

Case number:845813-2011857
Topic:Game: Tools
Opened by:jeff101
Status:Open
Type:Question
Opened on:Sunday, July 11, 2021 - 09:58
Last modified:Friday, August 27, 2021 - 19:33

Lately I have been forcing my protein designs into
unusual conformations, and when I check the "Show
backbone issues" box in the View Menu, I see many
red circles with white exclamation points in them.
When there are so many red circles, I find it hard
to count them all so I can tell if the recipes I 
am running are reducing their number. Because of 
this, I would like to find a way to automatically 
count them from within a Foldit LUA Recipe. Are 
there any LUA commands that tell if a particular 
segment has a backbone issue? Are there any that 
list the total # of backbone issues in the protein?

A related question is how Foldit decides which
segments have backbone issues. Does Foldit use
each segment's Backbone and Ideality subscores
to decide? If so, what ranges of these subscores
should give backbone issues?

Finally, if anyone can recommend good recipes for 
removing backbone issues while preserving the 
general shape of the protein, please let me know. 
My sense is that recipes using remix, rebuild, 
and/or idealize are good at removing backbone
issues, but it is tricky to remove them while
preserving the overall shape of the protein.

Thanks,
Jeff

(Sun, 07/11/2021 - 09:58  |  7 comments)


Joined: 09/24/2012
Groups: Go Science

Are the backbone issues reflected in the backbone subscores?

jeff101's picture
User offline. Last seen 24 min 26 sec ago. Offline
Joined: 04/20/2012
Groups: Go Science

That sounds reasonable and intuitive, but it would 
be good to have a member of the Foldit staff say so
officially.

Perhaps the answer is somewhere on the Foldit site
or its wiki pages, like in Josh's series of posts
about how to play Foldit.

jeff101's picture
User offline. Last seen 24 min 26 sec ago. Offline
Joined: 04/20/2012
Groups: Go Science

In Part 5 of Josh's "How to Foldit" series:
https://fold.it/portal/node/2010984#comment-43957
under "Visualization Options" and "Issues" it says:

Turning on “Show backbone issues” will point out 
places in your backbone that want to be Idealized. 
You can use Idealize or click the bubble to 
idealize the backbone: just watch out for the 
usual problems of Idealizing messing up other 
parts of your fold.

Backbone connection unideal. Click to fix or use 
the Idealize Tool.

jeff101's picture
User offline. Last seen 24 min 26 sec ago. Offline
Joined: 04/20/2012
Groups: Go Science

https://foldit.fandom.com/wiki/Score_part
has brief descriptions of the Backbone and 
Ideality subscores. It also lists names that 
Rosetta (REF2015) uses for them. 
-----------------------------------------------
For Backbone it says:

The backbone score part is based on the 
configuration of backbone atoms. The backbone 
score is directly affected by dihedral angles 
(see Dihedral angle).

REF2015 terms: rama_prepro, omega, p_aa_pp
-----------------------------------------------
Meanwhile, for Ideality it says:

The ideality score part is based on how close 
the bond lengths, angles, and torsion angles 
of the peptide bonds between residues are to 
ideal values. Torsion angles depend on atoms 
of preceding and following residues, so the 
ideality subscores of neighboring residues 
affect each other.

REF2015 terms: cart_bonded, yhh_planarity
-----------------------------------------------
Showing Backbone Issues with AAColor and 
Stick or Trace Line selected, the bottom
tip of each Backbone Issues symbol seems
to point to the border between 2 segments,
as if it refers to the connection between
those 2 segments instead of just one of
the 2 segments. Showing them with CPK and
Stick selected, each bottom tip seems to 
point to the border between one segment's
backbone nitrogen and the adjacent segment's
backbone carbonyl carbon (the carbon double
bonded to the backbone oxygen atom).

jeff101's picture
User offline. Last seen 24 min 26 sec ago. Offline
Joined: 04/20/2012
Groups: Go Science

The Foldit Wiki gives for REF2015 the 40-page pdf below:
https://daslab.stanford.edu/site_data/pub_pdf/2017_Alford_JCTC.pdf

jeff101's picture
User offline. Last seen 24 min 26 sec ago. Offline
Joined: 04/20/2012
Groups: Go Science

In the View Menu, if you hover your mouse over 
"Show backbone issues", it says "Show where the 
backbone has ideality and cis/trans problems."

I just Tabbed through Segment Information for 
a protein with several patches of red backbone 
issue symbols. Perhaps a good rule of thumb is 
that if two adjacent residues give Ideality 
subscores that total to a number more negative 
than -110, the border between these two residues 
is marked with a red backbone issue symbol. Is 
this how Foldit decides where to put the red 
backbone issue symbols? If not, then what is 
the rule that Foldit follows?

Next, I think the yellow backbone issue symbols 
are just between adjacent residues connected by 
cis peptide bonds. Is this correct?

Thanks!

jeff101's picture
User offline. Last seen 24 min 26 sec ago. Offline
Joined: 04/20/2012
Groups: Go Science
It would also help if when you hovered the cursor over a red 
or yellow backbone issue symbol, it listed which segments the 
backbone issue applied to. For example, you could change the 
red symbols' messages to something like below for a backbone
issue between segments 26 and 27:

Backbone connection from 26-27 is unideal. 
Click to fix or use the Idealize Tool.

Unideal backbone connection from 26-27.
Click to fix or use the Idealize Tool.
Sitemap

Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons