From: Daniel Fellner (
Date: Wed Jun 24 2020 - 22:36:42 CDT

The default 6-31G(d) gives a total convergence value of 1096.18 and the
following charges:

CK CE : 0.554
CL CD : -0.128
SM SC : -0.641

6-311+G(d) yields quite different charges but similar convergence,
converging to 1061.33 with charges:

CK CE: 0.710
CL CD: -0.143
SM SC: -0.782

I'm trying 6-31+G(d,p) now. Should the geometry minimisation be
recalculated at this level of theory too or just the single point MP2, HF
and water interaction calculations? I don't imagine the geometries would be
too different.

Kind regards,

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

On Tue, 23 Jun 2020 at 12:13, JC Gumbart <> wrote:

> Hi Daniel,
> At this point, I’m not sure what your issue might be. We have used HF in
> the past for sulfur without any apparent problems. Whether that’s
> “correct” or not, I don’t know. You might try comparing the energies and
> distances from Gaussian at different levels of theory. How different are
> they?
> Ultimately, parametrization is a lot of trial and error!
> Best,
> JC
> On Jun 22, 2020, at 3:09 AM, Daniel Fellner <>
> wrote:
> So from further reading it seems 3rd row and heavier element water
> interaction energies are computed at MP2/6-31G(d) level of theory and not
> scaled. As there isn't a way to do this in FFTK, does that mean FFTK
> shouldn't be used for compounds containing these elements?
> I've tried sticking to HF and using an expanded basis set with a diffuse
> function (HF/6-311+G(d)) but the convergence isn't much better
> *Daniel Fellner BSc(Hons)*
> PhD Candidate
> School of Chemical Sciences
> University of Auckland
> Ph +64211605326
> On Sat, 20 Jun 2020 at 14:55, Daniel Fellner <>
> wrote:
>> Ah thank you, I'll give that a try.
>> Charges are much more realistic now. The dipole and energies converge
>> very well (~5 and 50 respectively), though the distances are quite far off
>> (~1000 overall, and 0.5 – 1.5 individually). The major energy outliers are
>> the hydrogens vicinal to the sp3 oxygens, which if I weight at 0.5 does
>> improve the convergence, but not by much. If I then weight the overall
>> distance to 0.5 it proportionally helps the convergence (~500 overall). Not
>> sure how to strike the balance here.. Is there any particular rule as to
>> how much to weight outliers by? Or perhaps I need to rerun the calcs with
>> an expanded basis set after all?
>> *Daniel Fellner BSc(Hons)*
>> PhD Candidate
>> School of Chemical Sciences
>> University of Auckland
>> Ph +64211605326
>> On Sat, 20 Jun 2020 at 12:42, JC Gumbart <>
>> wrote:
>>> Only use the target data for the atoms you’re optimizing. It’s
>>> practically impossible for the optimizer to handle other atoms’ water
>>> interactions if it can’t adjust their charges.
>>> Best,
>>> JC
>>> On Jun 19, 2020, at 8:37 PM, Daniel Fellner <>
>>> wrote:
>>> I have tried that (excluding them from the charge groups list as per the
>>> hydrogens, but still using their water interaction data, right?) but the
>>> results are quite unrealistic. Or should I only be using the target data
>>> for the atoms I'm optimising?
>>> *Daniel Fellner BSc(Hons)*
>>> PhD Candidate
>>> School of Chemical Sciences
>>> University of Auckland
>>> Ph +64211605326
>>> On Sat, 20 Jun 2020 at 11:01, JC Gumbart <>
>>> wrote:
>>>> You should be *fixing* all charges with penalties < 10 and optimizing
>>>> only those with larger penalties.
>>>> You don’t need such tight bounds - that’s very likely the source of
>>>> your problem. The bounds are mainly to prevent absurdities, like a
>>>> negative hydrogen or a +4 carbon.
>>>> There’s also no need for a separate ESP calculation; the initial guess
>>>> is just that.
>>>> Best,
>>>> JC
>>>> On Jun 19, 2020, at 6:52 PM, Daniel Fellner <>
>>>> wrote:
>>>> 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
>>>> issue.
>>>> 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