From: Daniel Fellner (
Date: Fri Jun 19 2020 - 19:37:01 CDT

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