Russ,
just a few comments on your request:
First of all, atomic charges are a construct to mimick the electrostatic
properties and interactions of the atoms within the molecules, as you
probably know; therefore there is no 'correct' set atomic charges. Thus,
any set of atomic charges that 'works', i.e. that provide the
atoms/molecules/system with the necessary electrostatic properties, is
justified.
That said, your approach to derive atomic charges for a residue from a
related one may work.
In your case, however, I'd suggest to use the original RESP approach for
atomic charge generation, because this takes also some polarization or
charge relocalization effects into account: most probably, all side
chain atomic charges will affected by the missing methyl group.
The general approach for RESP atomic charge generation, i.e. charges
that best reproduce the electrostatic potential around the molecule, is
for non-standard amino acids in ff94/99/14:
- Generate at least two conformations (alpha/beta) of a sample peptide
(ACE-XXX-NME) and optimize it with a quantum chemistry program on the
HF/6-31G* level; avoid internal interactions in the structure.
- Ensure to have true minima in your structures, not a transition state.
- Use these minimized conformations to compute the electrostatic
potential (ESP) and do the charge fit according to the RESP procedure,
where additional constraints may be added (e.g. standard charges for
peptide bond atoms).
Doing so, your charge set will best reproduce the ESP of your two
conformations, and is consistent with the derivation of the atomic
charges of the other residues in the force field you use.
Have a look into the Amber tutorials and the manual for more info.
Furthermore, there exists Francois Dupradeau's RED server (running
PyRED) that allows you to compute the RESP charges for given
conformations in a reproducible way. It also allows for geometry
optimization as web service.
https://upjv.q4md-forcefieldtools.org/REDServer-Development/
Maybe that helps.
Best,
Anselm
Bioinformatik | NHR.FAU
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Germany
On 03/11/2022 06:19 PM, russ.brown.yahoo.com wrote:
> I request the help of someone who has expertise with the Amber force fields.
> I would like to perform NAB molecular dynamics for a protein that contains the non-standard amino acid, aminobutyric acid (ABA). Because ABA is a non-standard amino acid, I was unable find a force field that supports it. Hence, I modified the leaprc.ff99SB and all_amino94.lib files to include ABA. However, I have a question regarding the atomic charges that I assigned for ABA. Excerpts from the all_amino94.lib file are below.
>
> ABA is structurally similar to VAL but lacks one of the gamma methyl groups. Consequently, the beta carbon of ABA is bonded to two protons, similar to the beta carbon of LEU. Consequently, I used the 0.045700 charge of LEU HB2 and HB3 for the charges of ABA HB1 and HB2. Then I calculated the ABA CB charge of 0.095500 by decreasing the VAL CB charge of 0.298500 to 0.095500 so that the total charge of the ABA moiety remains neutral. Is this approach viable? If not, can someone please coach me in the proper technique for computing the charges for ABA?
> Thanks.
>
>
> !entry.LEU.unit.atoms table str name str type int typex int resx int flags int seq int elmnt dbl chg "N" "N" 0 1 131072 1 7 -0.415700
> "H" "H" 0 1 131072 2 1 0.271900
> "CA" "CT" 0 1 131072 3 6 -0.051800
> "HA" "H1" 0 1 131072 4 1 0.092200
> "CB" "CT" 0 1 131072 5 6 -0.110200
> "HB2" "HC" 0 1 131072 6 1 0.045700
> "HB3" "HC" 0 1 131072 7 1 0.045700
> "CG" "CT" 0 1 131072 8 6 0.353100
> "HG" "HC" 0 1 131072 9 1 -0.036100
> "CD1" "CT" 0 1 131072 10 6 -0.412100
> "HD11" "HC" 0 1 131072 11 1 0.100000
> "HD12" "HC" 0 1 131072 12 1 0.100000
> "HD13" "HC" 0 1 131072 13 1 0.100000
> "CD2" "CT" 0 1 131072 14 6 -0.412100
> "HD21" "HC" 0 1 131072 15 1 0.100000
> "HD22" "HC" 0 1 131072 16 1 0.100000
> "HD23" "HC" 0 1 131072 17 1 0.100000
> "C" "C" 0 1 131072 18 6 0.597300
> "O" "O" 0 1 131072 19 8 -0.567900
>
> !entry.VAL.unit.atoms table str name str type int typex int resx int flags int seq int elmnt dbl chg
> "N" "N" 0 1 131072 1 7 -0.415700
> "H" "H" 0 1 131072 2 1 0.271900
> "CA" "CT" 0 1 131072 3 6 -0.087500
> "HA" "H1" 0 1 131072 4 1 0.096900
> "CB" "CT" 0 1 131072 5 6 0.298500
> "HB" "HC" 0 1 131072 6 1 -0.029700
> "CG1" "CT" 0 1 131072 7 6 -0.319200
> "HG11" "HC" 0 1 131072 8 1 0.079100
> "HG12" "HC" 0 1 131072 9 1 0.079100
> "HG13" "HC" 0 1 131072 10 1 0.079100
> "CG2" "CT" 0 1 131072 11 6 -0.319200
> "HG21" "HC" 0 1 131072 12 1 0.079100
> "HG22" "HC" 0 1 131072 13 1 0.079100
> "HG23" "HC" 0 1 131072 14 1 0.079100
> "C" "C" 0 1 131072 15 6 0.597300
> "O" "O" 0 1 131072 16 8 -0.567900
>
> !entry.ABA.unit.atoms table str name str type int typex int resx int flags int seq int elmnt dbl chg
> "N" "N" 0 1 131072 1 7 -0.415700
> "H" "H" 0 1 131072 2 1 0.271900
> "CA" "CT" 0 1 131072 3 6 -0.087500
> "HA" "H1" 0 1 131072 4 1 0.096900
> "CB" "CT" 0 1 131072 5 6 0.095500
> "HB1" "HC" 0 1 131072 6 1 0.045700
> "HB2" "HC" 0 1 131072 7 1 0.045700
> "CG" "CT" 0 1 131072 8 6 -0.319200
> "HG1" "HC" 0 1 131072 9 1 0.079100
> "HG2" "HC" 0 1 131072 10 1 0.079100
> "HG3" "HC" 0 1 131072 11 1 0.079100
> "C" "C" 0 1 131072 12 6 0.597300
> "O" "O" 0 1 131072 13 8 -0.567900
>
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Received on Sun Mar 13 2022 - 04:00:03 PDT
