[Chimera-users] Ligand parametrization

[Eric Pettersen]

On Sep 4, 2012, at 5:40 AM, Miro Moman wrote:

> Hello,
> 
> When energy minimising protein-ligand complexes, I have observed that Chimera seldom, if ever, complains about missing parameters.
> 
> However, when I try to generate a Pmrtop file for the same complexes, quite often sLeap is unable to complete the request due to its inability to recognise certain atom types..
> 
> Provided that the minimization engine (MMTK) is using the Amber force filed, I was wondering:
> 
> Are parameters computed in the same way?
> 
> If not, what are the differences? Maybe a different forcefield version?

Parameters are not computed in the same way for Write Prmtop / sleap as they are for Minimize Structure / MMTK.

For Write Prmtop, Chimera relies on sleap's built-in parmchk to generate missing parameters.  sleap runs parmchk on a per-residue basis.  This means that parameters can be missing for bonds/angles/torsions that cross the boundary between the non-standard residue and any connected residues.  Since many non-standard residues are not connected to other residues (e.g. they are ligands), this isn't as big a problem as one might think, but it is still a problem.

For Minimize Structure, Chimera finds the entire connected chain that contains the non-standard residue and runs parmchk on that.  In fact, it runs it on all such chains at once.  This means that for structures that contain many chains with non-standard residues, the parmchk process can take a long time.  Nonetheless, the parmchk will produce a complete set of parameters.  We hope to make Chimera run parmchk on a per-chain basis sometime soon (parmchk execution time seems to scale exponentially with the number of atoms involved).

> In addition, is there a way to inspect the parameters that have been generated for minimising a given ligand or non-standard residue?

There is always a way.  Well, almost always.  There is this time at least!  You would need to edit Chimera's Python code so that it doesn't remove the parmchk output once it's done with it.

For Write Prmtop, there is a _clean function defined near line 95 of <your Chimera>/share/WritePrmtop/__init__.py.  You would add these lines at the beginning of the function to show the temp folder name in the reply log and to prevent it from being removed:

	print tempDir
	return
(indented appropriately)

Similarly, for Minimize Structure, there is a _removeTempDir function defined near line 301 of <your Chimera>/share/MMMD/MMTKinter.py.  Add these lines near the beginning of that function:

	print self.tempDir
	return
(also indented appropriately)

The frcmod file left in the temp dir has the generated parameters.  Other parameters are just the standard ones provided with the force field chosen.

--Eric

                        Eric Pettersen
                        UCSF Computer Graphics Lab
                        http://www.cgl.ucsf.edu


-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://plato.cgl.ucsf.edu/pipermail/chimera-users/attachments/20120904/36018dd8/attachment.html>