From: Bryan Roessler (
Date: Fri Oct 16 2015 - 10:01:53 CDT


Thank you very much for the reply. I should have included a second, related
question in my original query: since I am not going to include the
predefined atoms in the charge optimization step, is it still necessary to
calculate the individual water interactions for those atoms and include
them as input in the optimization?

Because it is necessary to include the known atoms from the bonded residue,
the complexity of the fragment also increases (~35 atoms total). As a
result, I've found that some of the waters will fly out of the Gaussian
optimization, presumably due to steric quantum interactions with the
surrounding atoms. I know that the preferred solution is to reduce the
complexity of the fragment by breaking it down further into its molecular
components (between aliphatic carbons) but I've found that the partial
charges that are assigned using this method do not reflect the
intermolecular charges well (possibly because the fragment contains an
ester). I think it is better to keep the fragment together as long as it is
OK to remove some of the errant water interaction calculations from the
optimization. What I don't entirely understand is if the water interactions
can be removed from the initial calculation (and thus not reflected in the
single-point energies of the entire fragment? I don't know) or need to be
removed only from the optimization step so that those atoms are still
included in the single-point calculations of the entire fragment.

In my trial and error, I have tried to calculate only the water
interactions for the atoms without existing FF charges, however when I
perform the optimization using this method, the charges on the atoms tend
to drift towards an integer charge.

Thanks again,


*Bryan Roessler | Graduate Research Assistant*
UAB | The University of Alabama at Birmingham
* <>*
Knowledge that will change your world

On Fri, Oct 16, 2015 at 2:50 AM, Mayne, Christopher G <>

> Bryan,
> Apologies for a delayed response; I have been traveling internationally.
> Yes, it is generally a good idea to include enough of the known atoms to
> cover the connection between known and unknown parameters. ffTK is
> designed so that it is easy to optimize a subset of parameters — in this
> case, retain the known parameters and optimize only the missing ones.
> For the specific case of charges, the typical method used is:
> 1) Set any “known” charges in the PSF file.
> 2) When setting the Charge Constraints (Opt. Charges -> Charge Constraints
> -> Charge Group) simply remove the known atoms from the constraints box.
> —> This process will optimize any atoms contained within the charge
> constraints while fixing the charge on the atoms that are not included in
> the box.
> When analyzing the optimization output, the raw objective function is not
> particularly informative. The COLP tool (available from Opt. Charges ->
> Results -> Open COLP) allows users to deconvolute the objective function
> and inspect each of the contributing terms. This allows you to judge which
> terms contribute the most to the objective function, and to identify
> problematic atoms.
> Regards,
> Christopher Mayne
> On Oct 13, 2015, at 9:08 PM, Bryan Roessler <> wrote:
> Hello,
> When parameterizing novel molecular fragments that will eventually be
> bonded to a residue with an existing forcefield, it is necessary to
> incorporate some of the atoms near the bond from the residue with existing
> forcefields that contribute to the dihedral, angle and bond parameters in
> the QM/MM optimization scheme.
> Is it then suggested that when performing the charge optimization step in
> fftk, I maintain the charges on those overlapping atoms as they exist in
> the CHARMM ffs as best as possible? In other words, should I create an
> upper and lower bound (so that the optimizer still has some 'play') that
> are very near the charge values on those atoms provided in the existing
> forcefield? Or should I let all of the charges optimize independently of
> the existing forcefield charge parameters?
> When I allow all of the charges to optimize without strict bounding, I can
> attain a total objective that is very near zero after several iterative
> optimization passes. However, when I loosely 'fix' the charges of some of
> the overlapping atoms that already exist in the forcefield, the charge
> optimization objective values are not nearly as good (which is to be
> expected as the degrees of freedom are reduced). However, in some cases the
> charges on the overlapping atoms can be quite different than the existing
> charge values in the the CHARMM ff if I let them optimize without
> restraints.
> Thanks for your help in advance,
> Bryan
> *Bryan Roessler | Graduate Research Assistant*
> UAB | The University of Alabama at Birmingham
> *
> <>*
> Knowledge that will change your world