From: Daniel Fellner (
Date: Fri Jun 19 2020 - 17:52:54 CDT

I have tried using MP2/6-31G(d) target data for the sulfur atoms only, it
did lead to slightly better convergence but it was still ~5000 with
relatively tight charge constraints. Perhaps the sulfur isn't the main

My charge optimisation procedure so far is this:

Set the initial charges to the CGenFF charges, except for the high penalty
(>10) atoms which I set to the MP2 ESP (computed separately) charges. I set
charge constraints of +/- 0.2 from CGenFF or MP2 charges, whichever gave
the biggest range. For target QM data I excluded one 120 degree carbonyl
interaction from each of the two carbonyls (the molecule is symmetrical and
one side of the carbonyls are hindered). All the other waters settle at
reasonable distances, so I have basically a full set of good water
interaction data.

I've tried adjusting the weights of more poorly converging atoms, and it
does improve the objective function but I get nonsense. I think there are
probably too many poorly-converging atoms. The carbonyl oxygens perform the
worst, though some of the hydrogens have issues too. There are instances
with hydrogens on the same carbon: one of them converges fine, the other
doesn't – with no steric hindrance and the water distances look the same.

If you wanted some idea of the structure - it's the product of the reaction
between divinyl malonate and two ethanethiols (a model for two cysteines).

I'll try playing with the basis sets, thanks for the suggestions!

*Daniel Fellner BSc(Hons)*
PhD Candidate
School of Chemical Sciences
University of Auckland
Ph +64211605326

On Sat, 20 Jun 2020 at 08:08, JC Gumbart <> wrote:

> From
> “The final class of interactions, involving sulfur atoms and sp hybridized
> carbon and nitrogen atoms (orange circle), are systematically shorter than
> the target data. With the sp carbon atoms, it was found that this
> shortening was necessary to obtain good bulk solvent properties and, in the
> case of nitrogen, to reproduce QM water interaction data for the linear
> complex. We speculate that this is due to the fact that a diffuse electron
> cloud surrounds sp centers in all directions except along the bond axis.
> Similarly, for the sulfur atoms, the discrepancy in hydrogen bond distance
> is due to the increased radii and diffuse character of these atoms. When
> this class of functional groups was initially parametrized, it was found
> that the HF/6–31G(d) level of theory and its standard scaling and
> offset rules were not appropriate, and it was necessary to apply the
> MP2/6–31G(d) level of calculation for the interactions with
> water. Subsequently, it was found that the MM minimum interaction distances
> had to be significantly shorter than the corresponding QM distances at this
> level of theory, in order to obtain the correct pure solvent properties
> (A.D. MacKerell, Jr., unpublished). “
> And in the Figure 7 caption: “The QM level of theory is MP2/6–31G(d) for
> model compounds containing sulfur atoms and scaled HF/6–31G(d) for all
> remaining compounds."
> This implies to me that no scaling was applied to the MP2 interaction
> energies. As for the shift, we are generally fine with reducing the
> distance interaction weight to, say, 0.5.
> One thing to note, I’m not sure you can get the right interaction energy
> with FFTK when you start mixing QM levels of theory. We use the compound
> HF and water HF runs in order to subtract off their individual energies
> from the total in the combined runs. If these are run at different levels
> of theory, it’ll probably give nonsense. Proceed with extreme caution.
> Other things to look at: are all your water interactions reasonable? Or
> do the waters fly away in some of them?
> You could also try expanding the basis set or add diffuse functions, still
> with HF, as long as you do it for all QM runs.
> Best,
> JC
> On Jun 19, 2020, at 12:17 AM, Daniel Fellner <>
> wrote:
> Hi all,
> In the CGenFF papers, it mentions that compounds with sulfur were run at
> MP2/6-31G(d) level of theory. I've been having trouble getting the
> objective function to fit using the HF/6-31G(d) water data, so I thought I
> would try it with MP2.
> I was wondering, do the water shift (-0.2) and scale (1.16) settings need
> to be changed? And should I just give FFTK the location of the MP2 file
> where it asks for HF? And use an MP2 calculation of the water-sp?
> Also, I've seen it mentioned in the CHARMM forums that the distances
> aren't actually considered in the original CGenFF procedure, and I
> certainly get much better convergence if I turn the distance weight down. I
> wonder how this would relate to sulfur-containing compounds?
> *Daniel Fellner BSc(Hons)*
> PhD Candidate
> School of Chemical Sciences
> University of Auckland
> Ph +64211605326