[Chimera-users] Linking two chains in a PDB file

[Elaine Meng]

Hi Gerald,
Yes, but ... probably not without making the structure very bad, in a way that may or may not be rescuable.  You can add a bond between two atoms that is 50 angstroms long if you want, with Build Structure or the "bond" command.  (The two atoms have to be in the same model before you can bond them.)  You could even try rotating torsions within the linker manually to try to make the other end of it closer to the desired destination point.  In my experience, however, trying to manually fulfill multiple constraints (reasonable phi/psi as well as endpoint locations and not running into other atoms) is extremely difficult and frustrating.  You could try energy-minimizing the result, maybe even letting only the atoms within the linker move.  Again caveats: minimization has extremely limited ability to improve a mangled structure, as it will only go "downhill" and not climb even small barriers that need to be surmounted on the way to a reasonable structure.  It depends whether there is clear downhill path to a reasonable structure, and this may not be the case for any complicated building.

In my opinion, modeling like this is better done with software that performs conformational sampling (dynamics or just combinatorics) in the presence of constraints and/or restraints.

It also depends on what you plan to do with the result; if it's just going to be a schematic, you would worry less than if you are trying to do something quantitative like rationalize binding affinities.

If everything were peptidic (i.e. ligand + linker + ligand = one peptide) perhaps it could be done with Modeller's loop-building capability.  In other words, Modeller could propose multiple linker conformations as if it were a loop between the peptides on either end.  You would give it the full sequence and it would fill in the gap with possible structures.  Chimera includes interfaces to Modeller:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/modeller.html>

However, it sounds like your ligands are organic molecules but not peptides.  Sorry I couldn't give a rosier picture,
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco

On Aug 9, 2013, at 1:44 PM, Maxwell Cherf wrote:

> Hi Elaine,
> 
> Thank you for your reply! I was able to attach both ligands using the split command followed by the join command. 
> 
> I have another problem now though -  my goal is to build a peptide linker that attaches the termini of two ligands that are bound to a receptor (the PDB contains three protein structures) ; I also want both ligands to remain properly docked to the receptor while I incorporate the linker. Using the slit/join commands allowed me to link both ligands, but ended up changing their orientation relative to the receptor. Is there a way to build a peptide linker that attaches the termini of the two ligands without changing their orientation using Chimera?
> 
> Thanks again,
> Gerald