From: JC Gumbart (gumbart_at_physics.gatech.edu)
Date: Fri Jun 19 2020 - 19:42:54 CDT

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 <dfel694_at_aucklanduni.ac.nz> 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 <gumbart_at_physics.gatech.edu <mailto:gumbart_at_physics.gatech.edu>> 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 <dfel694_at_aucklanduni.ac.nz <mailto:dfel694_at_aucklanduni.ac.nz>> 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 <gumbart_at_physics.gatech.edu <mailto:gumbart_at_physics.gatech.edu>> wrote:
>> From https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888302/ <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888302/>
>>
>> “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 <dfel694_at_aucklanduni.ac.nz <mailto:dfel694_at_aucklanduni.ac.nz>> 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
>>
>