From: Daniel Fellner (
Date: Mon Jun 22 2020 - 02:09:39 CDT

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 <>

> 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