From: Bryan Roessler (
Date: Mon Oct 19 2015 - 09:45:32 CDT

I'm going to take a stab and try to answer my own question based on some
further observations.

I believe that it is necessary to remove any waters that do not reach a
proper minimized state (for instance if they fly out of the Gaussian
simulation). It is best to try and include as many water interaction target
files as possible for the fragment (even for atoms that have predefined
charges), but if some of them skew the optimization results (for instance,
if they are not near the energy objective in COLP), then it is best to
reduce their weighting in the calculation or to remove them altogether.

Following these guidelines I have been able to get realistic optimized
charges near the CGenFF predictions.

If I am in error, please let me know.



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

On Fri, Oct 16, 2015 at 10:01 AM, Bryan Roessler <> wrote:

> Christopher,
> 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
> *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 <
>> wrote:
>> 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