[Chimera-users] Linking two chains in a PDB file
maxcherf at gmail.com
Fri Aug 9 19:19:12 PDT 2013
Using modeller sounds like the exact solution I'm looking for. Both the
ligands and the linker I will connect them with are peptides.
I tried using modeller, but I haven't gotten it to work yet. Here's what
1. built peptide linker using the "build structure" function
2. attached the linker to one ligand1 using the "join" function
3. combined the ligand1-linker with the second ligand into one model using
the "combine" function
4. added an unrealistic ~40 angstrom bond between the linker and second
ligand (now we have ligand1 - linker - 40A bond - ligand 2, all in one
5. I then tried using the "model/refine loop" function to find acceptable
orientations for the linker (including the 40A bond) I incorporated, but I
was unable to do this because the two ligands were still separate chains,
and the "model/refine loop" function requires them to be in the same chain.
If I use the "join" command instead of the "combine" command to attach the
ligand1-linker to ligand2, I get one chain and then the model/refine loop
function works perfectly to remodel the linker. However, using the join
function changes the orientation of the ligands relative to the receptor,
and I need the ligands to remain docked properly to the receptor.
Is there a way to join both ligands into the same chain without changing
their orientation? Or, do you know of an alternate approach for adding a
linker between the two ligands without changing their orientation using
On Fri, Aug 9, 2013 at 4:31 PM, Elaine Meng <meng at cgl.ucsf.edu> wrote:
> 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:
> However, it sounds like your ligands are organic molecules but not
> peptides. Sorry I couldn't give a rosier picture,
> 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
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