Dear Anselm,
Merry (belated) Christmas! Thanks for your explanation; it makes much sense.
To be consistent across a series of structures, then, I’m thinking of deriving the charges for the standard Tyr and modified Tyr for the same set of conformations.
In my workflow, I only held the phi and psi angles fixed (e.g. "opt=modredundant" in the Gaussian input), but I’ll still check the backbone-sidechain interactions.
Thanks for confirming that the overall workflow looks fine.
Best,
Matthew
> On Dec 29, 2021, at 4:57 AM, Dr. Anselm Horn <anselm.horn.fau.de> wrote:
>
> *Message sent from a system outside of UConn.*
>
>
> Merry Christmas
>
>
> Dear Matthew,
>
> the reason for the discrepancies in the different charge sets certainly
> results from the fact that different input structures were used for the
> QM-ESP calculations, i.e. your structures are (a bit) different from
> those used for the original charge derivation. Since you know that the
> QM-ESP is (very) sensitive to the molecular structure, you'd need the
> exact same two molecular structures in order to obtain the same RESP
> charges.
>
> In your case, you created two dipeptides via leap and adapted the
> backbone angles accordingly, and these structures you directly submit to
> ESP calculation without any prior geometry optimization: your structures
> are just based on the leap-template.
>
> Thus, a different result for RESP charges might be expected, if one uses
> structures different from those used for the original derivation.
>
> Having said this, I'd like to refer to prior discussions on this list
> about that topic, where it had debated how to re-do the original
> calculations.
>
> For your own work, I think that the basic workflow seems ok to me, with
> the exception, however, that you should have a closer look at your
> structures: You might want to relax them via QM geometry optimizations,
> check for true minima, and ensure via visual inspection that there's no
> self-interaction between the sidechain an the mainchain atoms, which
> would disturb your ESP. For very large and uncommon sidechains, you may
> want to include not only two conformers but more.
>
> Since there are many publications with additional parameterizations, I
> recommend reading the respective methods sections and supplement files.
> (Unfortunately, parameter derivation is not always described in such a
> detail that would allow simple repetition.)
>
> Hope that helps
>
> Anselm
>
> Bioinformatik | NHR.FAU
> Friedrich-Alexander-Universität Erlangen-Nürnberg
> Germany
>
>
> On 12/29/2021 05:54 AM, Matthew Guberman-Pfeffer wrote:
>> Dear Amber Community,
>>
>> I need to parameterize modified amino acids. As a reference, I tried to learn the procedure by applying the below steps to derive the charges for Tyr, but I get charges very different from what is given in FF14SB. Am I doing something wrong? If not, how can I make comparisons between simulations using the FF14SB charges for Tyr and simulations with my modified Tyr, if the procedure for the latter can’t reproduce the charges for the former?
>>
>> Step #1: Build ACE-TYR-NME capped peptide with LEaP.
>> Step #2: Generate alpha-helix and beta-sheet Conformers by setting phi/psi angles with CPPTRAJ
>> Step #3: Convert mol2 from CPPTRAJ for each conformer to Gaussian input and run with the route line: #p opt=modredundant freq hf/6-31g(d) pop=mk iop(6/33=2,6/42=6)
>> where I’ve defined the phi/psi angles to be fixed at the canonical alpha-helix or beta-sheet values.
>> Step #4: Extract ESP data from Gaussian output with espgen and concatenate results for alpha-helix and beta-sheet conformers.
>> Step #5: Run residuegen with the below input file, in which I’ve specified the charges of the backbone N, H, C, and O atoms to be the values found for TYR in ff14SB.
>>
>>
>> INPUT_FILE TYR.ahelix.ac
>> CONF_NUM 2
>> ESP_FILE TYR.esp
>>
>> SEP_BOND N1 C2
>> SEP_BOND C11 N2
>>
>> NET_CHARGE 0
>>
>> ATOM_CHARGE N1 -0.4157
>> ATOM_CHARGE H4 0.2719
>> ATOM_CHARGE C11 0.5973
>> ATOM_CHARGE O3 -0.5679
>>
>> PREP_FILE: TYR.prep
>> RESIDUE_FILE_NAME: TYR.res
>> RESIDUE_SYMBOL: TYR
>>
>>
>> Below is the comparison of the charges in ff14SB versus what I obtain:
>>
>> TYR (ff14SB TYR (residuegen)
>> -0.4157 -0.4157
>> 0.2719 0.2719
>> -0.0014 -0.0942
>> 0.0876 0.1087
>> -0.0152 0.7629
>> 0.0295 -0.2468
>> 0.0295 -0.2468
>> -0.0011 -0.0982
>> -0.1906 -0.0371
>> 0.1699 -0.0366
>> -0.2341 -0.0314
>> 0.1656 0.0017
>> 0.3226 0.1955
>> -0.5579 -0.2451
>> 0.3992 0.1849
>> -0.2341 -0.0314
>> 0.1656 0.0017
>> -0.1906 -0.0371
>> 0.1699 -0.0366
>> 0.5973 0.5973
>> -0.5679 -0.5679
>>
>>
>> Please let me know if you need more information to help me with this matter.
>>
>> Best,
>> Matthew
>>
>>
>>
>>
>>
>>
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Received on Wed Dec 29 2021 - 10:30:02 PST
