[chimerax-users] Refine predicted structure by pulling

[Roden Deng Luo]

Hi Tristan and Tom,

Thanks very much! Very appreciated! I did play with ISOLDE with the
mentioned guidance. I faced the same issues as mentioned by Tom. I thought
I should try it a few more times and then reply.

So, I encountered this "at least one residue in your model does not match
any templates in the MD forcefiled" warning first; and then it asked me to
"addh". And then the same as Tom mentioned. The force I have is more of a
"directional" force. I wonder is it possible to have a torque force? Or, is
it possible to set a group of amino acids as one rigid body?

Very appreciate the fiddling (manual modeling) guidance too.

Roden


On Mon, Oct 25, 2021 at 10:02 PM Tom Goddard <goddard at sonic.net> wrote:

> Hi Roden, Tristan,
>
>   I tried Tristan's suggestion for straightening the long AlphaFold helix
> model.  It didn't work well for me because the restraints were too soft, so
> if I pulled on the first 160 residues it hardly moved the attached 2000 and
> instead just distorted the linker.  Tristan is there a way to make the
> restraints much stiffer?  I see the "isolde restrain distance" command has
> a "kappa" option and "falloff" option but I don't know if kappa is a
> stiffness or what magnitude it usually uses.
>
>   I think a better approach is to just rigidly rotate and translate large
> straight sections by hand using the "Move atoms" mouse mode in the ChimeraX
> 1.3 toolbar tab called Right Mouse.  I tried this and have attached an
> image of about 10 minutes fiddling by hand.  I hover the mouse at a hinge
> residue to get the residue number and then select everything on one side of
> that hinge "select :1182-2419" then use the right mouse button in the "move
> atoms" mode, holding the shift key down to do rotations, and no shift key
> to do translations.  I zoom in on the hinge to try to adjust so the bond is
> not stretched and to avoid clashes.  It would probably take 1 hour to do a
> good job.  With my 10 minute test I then saved an mmCIF file and tried in
> ChimeraX 1.2.5 to minimize it with ISOLDE, but it said there were severe
> clashes.
>
>     Tom
>
>
>
> On 10/24/2021 1:49 AM, Tristan Croll via ChimeraX-users wrote:
>
> Hi Roden,
>
> This should be reasonably straightforward with the ISOLDE plugin (
> https://cxtoolshed.rbvi.ucsf.edu/apps/chimeraxisolde
> <https://urldefense.com/v3/__https://cxtoolshed.rbvi.ucsf.edu/apps/chimeraxisolde__;!!Nmw4Hv0!jtJ8dNnTQ0tJc0CLw8HqKh7NIbLUHH72Nc6AJZpi2582f8VOx0v-FbJqs87FyKfCyVw$>).
> You'll also want to be working on a machine with a good GPU to make it
> feasible for a model this size. It'll be easier still with the new release
> coming in a few weeks, which has some added tools specifically for working
> with AlphaFold models. But with care you could do it now:
>
>
>    - first, check carefully for entanglement between distant domains
>    (this is an issue for AlphaFold with these very long, flexible proteins -
>    if distant parts of the protein have no coevolutionary signal they don't
>    really "know" about each other and can end up trying to occupy the same
>    space). Looks like your particular example is free of that problem.
>    - Start ISOLDE. Then, assuming your protein is model #1, do the
>    following commands:
>       - isolde restrain distances #1 distanceCutoff 5
>       - isolde restrain torsions #1 angleRange 60
>       - isolde sim start #1
>    - Then, you'll want to use the "tug selection" mouse mode (third from
>    bottom right of the ISOLDE panel). Make a selection for a suitable region
>    to tug (e.g. "sel #1-100 at CA" to tug the N-terminus), and tugging
>    forces applied by right-click-and-drag will be spread over that selection.
>    Keep a close eye on the distance restraints - if they start to become too
>    strained (lots of purple appearing), stop tugging and let the model settle.
>    - If you have unwanted distance restraints between domains that should
>    be distant from each other, you can selectively release restraints on
>    selected atoms with "isolde release distances sel".
>    - You might find it easier for a job like this to reduce the view to a
>    C-alpha trace - just "hide ~@CA" - if you do this after you've started a
>    simulation, it'll automatically revert to the all-atom view once you stop.
>
> Happy modelling!
>
> -- Tristan
>
> ------------------------------
> *From:* ChimeraX-users <chimerax-users-bounces at cgl.ucsf.edu>
> <chimerax-users-bounces at cgl.ucsf.edu> on behalf of Roden Deng Luo via
> ChimeraX-users <chimerax-users at cgl.ucsf.edu> <chimerax-users at cgl.ucsf.edu>
> *Sent:* 23 October 2021 16:30
> *To:* chimerax-users at cgl.ucsf.edu <chimerax-users at cgl.ucsf.edu>
> <chimerax-users at cgl.ucsf.edu>
> *Subject:* [chimerax-users] Refine predicted structure by pulling
>
> Dear ChimeraX Users,
>
> There is this AlphaFold prediction:
> https://alphafold.ebi.ac.uk/entry/P02549
> <https://urldefense.com/v3/__https://alphafold.ebi.ac.uk/entry/P02549__;!!Nmw4Hv0!jtJ8dNnTQ0tJc0CLw8HqKh7NIbLUHH72Nc6AJZpi2582f8VOx0v-FbJqs87FZ78SQ3E$>.
> And we know this protein should be more or less in a rod-like shape rather
> than a globular shape: https://en.wikipedia.org/wiki/Spectrin
> <https://urldefense.com/v3/__https://en.wikipedia.org/wiki/Spectrin__;!!Nmw4Hv0!jtJ8dNnTQ0tJc0CLw8HqKh7NIbLUHH72Nc6AJZpi2582f8VOx0v-FbJqs87F7tqKeq8$>
> and related literature such as
> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218374/
> <https://urldefense.com/v3/__https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218374/__;!!Nmw4Hv0!jtJ8dNnTQ0tJc0CLw8HqKh7NIbLUHH72Nc6AJZpi2582f8VOx0v-FbJqs87FiXfOrTA$>.
> I wonder is there a way that we can pull the two ends of the predicted
> structure while maintaining the secondary structures, mostly alpha-helices
> in this case, inside ChimeraX?
>
> I am quite new to ChimeraX. I understand this is more fitted to an MD
> simulation. But I got to know there are options to fit a PDB to a density
> map. So I wondered if this can be achieved in ChimeraX.
>
> Best,
> Roden
>
> ------------------------------
> This message and its contents, including attachments are intended solely
> for the original recipient. If you are not the intended recipient or have
> received this message in error, please notify me immediately and delete
> this message from your computer system. Any unauthorized use or
> distribution is prohibited. Please consider the environment before printing
> this email.
>
> _______________________________________________
> ChimeraX-users mailing listChimeraX-users at cgl.ucsf.edu
> Manage subscription:https://www.rbvi.ucsf.edu/mailman/listinfo/chimerax-users <https://urldefense.com/v3/__https://www.rbvi.ucsf.edu/mailman/listinfo/chimerax-users__;!!Nmw4Hv0!jtJ8dNnTQ0tJc0CLw8HqKh7NIbLUHH72Nc6AJZpi2582f8VOx0v-FbJqs87F2XryFwk$>
>
>
>

-- 

This message and its contents, including attachments are intended solely 
for the original recipient. If you are not the intended recipient or have 
received this message in error, please notify me immediately and delete 
this message from your computer system. Any unauthorized use or 
distribution is prohibited. Please consider the environment before printing 
this email.
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://plato.cgl.ucsf.edu/pipermail/chimerax-users/attachments/20211025/76052523/attachment-0001.html>
-------------- next part --------------
A non-text attachment was scrubbed...
Name: Needs_torque.png
Type: image/png
Size: 684001 bytes
Desc: not available
URL: <http://plato.cgl.ucsf.edu/pipermail/chimerax-users/attachments/20211025/76052523/attachment-0003.png>
-------------- next part --------------
A non-text attachment was scrubbed...
Name: addh.png
Type: image/png
Size: 60181 bytes
Desc: not available
URL: <http://plato.cgl.ucsf.edu/pipermail/chimerax-users/attachments/20211025/76052523/attachment-0004.png>
-------------- next part --------------
A non-text attachment was scrubbed...
Name: Snipaste_2021-10-24_20-37-39.png
Type: image/png
Size: 19775 bytes
Desc: not available
URL: <http://plato.cgl.ucsf.edu/pipermail/chimerax-users/attachments/20211025/76052523/attachment-0005.png>