[Chimera-users] Homology modelling with Chimera/Modeller

[Y Y]

Hi Elaine:

Thanks a lot. I'll give it a try.

Best Regards

TW

On Tue, Feb 16, 2021 at 11:40 AM Elaine Meng <meng at cgl.ucsf.edu> wrote:

> Hi TW,
> If you have a template for the whole multichain complex (all the template
> chains together in a single structure in the desired locations relative to
> each other), you may be able to do it with the Modeller interface in
> ChimeraX instead of Chimera.  However, if you don't have a template that
> includes the Fc in the proper spatial relationship to the other receptor
> and ligand, Modeller is not going to make it up for you.  Instead you would
> need to predict that using some kind of protein-protein docking method, or
> just place them by hand if you have a good enough idea of how they are
> supposed to interact.  Chimera and ChimeraX do not have protein-protein
> docking tools, other than hand placement.
>
> For multichain modeling, you would also need a sequence opened in ChimeraX
> for each unique chain, with the template structure for that chain
> associated with that sequence.
>
> For multichain Modeller with ChimeraX, see:
> <https://www.rbvi.ucsf.edu/chimerax/features.html#multichain-modeller>
> <https://www.rbvi.ucsf.edu/chimerax/docs/user/tools/modeller.html>
>
> I hope this helps,
> Elaine
> -----
> Elaine C. Meng, Ph.D.
> UCSF Chimera(X) team
> Department of Pharmaceutical Chemistry
> University of California, San Francisco
>
>
> > On Feb 16, 2021, at 10:22 AM, Y Y <yong.yin at staidsonbio.com> wrote:
> >
> > Hi Elaine:
> >
> > Thanks very much for your explanation.
> >
> > Indeed, I am trying to model a Fc fusion protein with two chains.
> Besides Fc having 3D structures, the other receptor and ligand have their
> 3D complex structures. In such a case, can the Modeller (eg. Modeller 9.24
> version) alone do the modeling job?
> >
> > I highly appreciate your help.
> >
> > Best regards
> >
> > TW
> >
> > On Tue, Feb 16, 2021 at 9:31 AM Elaine Meng <meng at cgl.ucsf.edu> wrote:
> > Hi TW,
> > The Chimera interface to Modeler is simplified so you cannot necessarily
> do any type of modeling that might be possible if you used Modeller
> directly.  I'm not completely sure either of the following would work, but
> possible things to try:
> >
> > (A) open all the separate template structures and if they don't
> associate automatically, use the Multalign Viewer (sequence viewer window)
> associations dialog to manually associate all of the structures to your
> single long fusion sequence.  Then you can choose all of them as templates.
> >
> > However, the modeling may not pay attention to the current relative
> positions of these domains in the structures.  They might be modeled in
> different orientations not interacting with each other.
> >
> > (B) If the PDB structures are already the correct sequences and all you
> are trying to do is connect them with linkers without moving them relative
> to each other, a different approach to try would be to first combine all
> the parts you want in your fusion into a single chain in a single model
> (e.g. see Model Panel function copy/combine).  Then associate that single
> chain (which will have missing segments, the linkers) with your long fusion
> sequence.  Then use the "missing loops" option of the Chimera Modeller
> interface to try to fill them without moving the existing parts relative to
> each other.
> >
> > If I misunderstood you and you are actually trying to model a complex of
> more than one chain (not just one single fusion chain), you can't use the
> Chimera interface for Modeller for that.  The interface only models single
> chains.
> >
> > I hope this helps,
> > Elaine
> > -----
> > Elaine C. Meng, Ph.D.
> > UCSF Chimera(X) team
> > Department of Pharmaceutical Chemistry
> > University of California, San Francisco
> >
> >
> > > On Feb 13, 2021, at 2:38 PM, StaidsonBio <yong.yin at staidsonbio.com>
> wrote:
> > >
> > > Hi:
> > >
> > > I am trying to do homology modelling with Chimera/Modeler for a Fc
> fusion protein, which contains three domains, one is Fc, one is receptor
> and the 3rd is ligand. Fc has many PBD structures in PDB database and the
> receptor has couple of 3D structures with the ligand as well. I used the
> fusion protein sequence to do blast in Chimera and it gave matched sequence
> files to Fc domain only, no sequence files for the receptor-ligand complex,
> even it already has couple of solved 3D crystal structure files in PDB
> database. Is there any suggestion about this issue? Can I do separately,
> use Fc domain alone as search sequence for its template and use
> receptor-ligand sequences as search sequence for its template? If it is ok,
> there are two template files. How to make them into one template file for
> modelling late?
> > >
> > > Thanks very much for your suggestion.
> > >
> > > Sincerely
> > >
> > > TW
> > >
>
>
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