[chimerax-users] polymer modeling and conjugation

[Elaine Meng]

Hi Victor!
This answer discusses both Chimera and ChimeraX...although there is a  separate chimera-users at cgl.ucsf.edu address for Chimera questions, you don't need to re-send; I will try to answer your questions here for both.

(1 & 2) For biopolymers, Chimera can build peptides of any length, or  helical  DNA, RNA, DNA/RNA.  It does not predict the conformation, though -- you have to tell it what  peptide backbone angles you want.  It is not really intended for building other types of organic polymers, although you can do it "manually" with lots of steps, by gradually adding atoms/bonds.  You can "conjugate" by joining models, which just means adding a bond between two molecules that were previously separate.  See Chimera "Build Structure" tool, with parts including Start Structure, Modify Structure, Join Models, etc.  
<https://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/editing/editing.html>

ChimeraX also has a Build Structure tool but it doesn't have all the parts of the Chimera one yet.  It doesn't have Join Models section, for example.
<https://rbvi.ucsf.edu/chimerax/docs/user/tools/buildstructure.html>

Organic polymer building may be somewhat tedious and inefficient in Chimera.  If there were some other tool good for building organic polymers you might use that instead, and then import it (e.g. PDB file) into Chimera for joining to the antibody  structure.

I haven't modeled organic polymers in general (other than proteins and nucleic acids) so I'm not familiar with what other programs one would use to build them, sorry.  Probably there are many relevant programs and maybe even webservers to do that.

(3) Seems like Chimera is more likely to be able to build it than ChimeraX currently, so there is no export issue.  However, I don't see how you could use MD ensemble since there would just be one structure, not an ensemble.  Maybe you meant Chimera's molecular dynamics simulation tool?  Just be aware that that tool was developed for small molecule simulations and has many limitations. See the boxed warning on its help page:
<https://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/md/md.html>

Also it may have problems assigning simulation parameters to the polymer moiety and  to the bond between it and the protein.

 For thorough analysis of complex macromolecular structures and medium- to longer-length simulations, you may need to use some other package like AMBER or GROMACS instead of Chimera.

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Nov 11, 2021, at 8:00 AM, Victor Ejigah via ChimeraX-users <chimerax-users at cgl.ucsf.edu> wrote:
> 
> Hi Elaine,
>               I am using chimeraX for protein analysis and simulations and recently, we have a question we want to explore by first simulating before going to the wet lab. We want to conjugate a polymer of different molecular weight to an antibody and thereafter determine the impact of the MW of each polymer on the binding affinity of the mAB to its ligand. Therefore, we want to know
> 1) Can we create polymers of different sizes with chimera? If not, can you recommend alternatives?
> 2) What tool can we use for conjugation( assuming chimera can be of help)?
> 3) Can such conjugates be exported to Chimera1.5 for MD ensemble since Chimera X does not have this feature?
> I will be most glad to hear from you soon.
> Kind regards,
> Victor (PhD student @Howard University)