Xianwei,
as you already identified, the obvious problem is the 'interface'
between the new residue and the existing flanking residues: Since you
used gaff atom types for the new residue and not the normal protein
force field types, you had to provide these information in addition.
It may be, however, more consistent, to assign and use protein atom
types for TYD, since you describe the rest of your system with such a
force field, too. Thus, you could manually change the atom types within
the workflow suggested by Todd to something more TYR-like.
Running parmchk2 then again would mark you any missing parameters.
Note, however, that the bcc atomic charges, you created via tleap on
your truncated mid-chain residue, are not consistent with the rest of
the force field; especially the atomic charges of the peptide group
atoms are uniform in the protein force fields.
It is up to you to decide whether the parameters you created fit your
needs, and this depends on the importance of the TYD residue in your
study. Thus, you may want to run test simulations to validate your
parameter set.
(Maybe there are parameters for TYD available in previous publications.)
Best,
Anselm
Bioinformatik | NHR.FAU
Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Germany
Am 03.11.2023 um 04:17 schrieb Xiangwei Zhu via AMBER:
> Thanks for the detailed instructions, Todd. I can reproduce them and generate the exact same TYD.prepi and TYD.frcmod. But I got errors when trying steps 5 through 8 on my own pdb file. Errors were mostly related to the missing of bond, angle, and torsion parameters between atoms from TYD and its neighbor residues. Not sure what was missed. Below is an example pdb file. Could you please give it a try? Thanks,
>
> Xiangwei
>
> test.pdb
> --------------------------------------------------------------------------------
> ATOM 1 H1 ACE 1 9.555 -90.040 -55.409 1.00 0.00
> ATOM 2 CH3 ACE 1 9.163 -91.057 -55.409 1.00 0.00
> ATOM 3 H2 ACE 1 9.511 -91.581 -54.519 1.00 0.00
> ATOM 4 H3 ACE 1 9.511 -91.581 -56.299 1.00 0.00
> ATOM 5 C ACE 1 7.633 -91.057 -55.409 1.00 0.00
> ATOM 6 O ACE 1 7.009 -89.998 -55.409 1.00 0.00
> ATOM 7 N VAL 2 8.685 -91.044 -54.603 1.00 0.00
> ATOM 8 H VAL 2 9.629 -90.978 -54.955 1.00 0.00
> ATOM 9 CA VAL 2 8.494 -91.237 -53.173 1.00 0.00
> ATOM 10 HA VAL 2 7.432 -91.250 -52.939 1.00 0.00
> ATOM 11 CB VAL 2 9.048 -92.578 -52.653 1.00 0.00
> ATOM 12 HB VAL 2 10.103 -92.620 -52.699 1.00 0.00
> ATOM 13 CG1 VAL 2 8.890 -92.661 -51.144 1.00 0.00
> ATOM 14 HG11 VAL 2 9.159 -93.660 -50.798 1.00 0.00
> ATOM 15 HG12 VAL 2 9.541 -91.948 -50.636 1.00 0.00
> ATOM 16 HG13 VAL 2 7.851 -92.460 -50.881 1.00 0.00
> ATOM 17 CG2 VAL 2 8.342 -93.746 -53.324 1.00 0.00
> ATOM 18 HG21 VAL 2 8.546 -93.745 -54.395 1.00 0.00
> ATOM 19 HG22 VAL 2 8.706 -94.687 -52.910 1.00 0.00
> ATOM 20 HG23 VAL 2 7.265 -93.677 -53.164 1.00 0.00
> ATOM 21 C VAL 2 9.087 -90.084 -52.385 1.00 0.00
> ATOM 22 O VAL 2 10.280 -89.810 -52.465 1.00 0.00
> ATOM 23 N TYD 3 8.230 -89.400 -51.637 1.00 0.00
> ATOM 24 H TYD 3 7.256 -89.665 -51.618 1.00 0.00
> ATOM 25 CA TYD 3 8.658 -88.287 -50.811 1.00 0.00
> ATOM 26 HA TYD 3 9.629 -87.912 -51.138 1.00 0.00
> ATOM 27 CB TYD 3 7.653 -87.143 -50.912 1.00 0.00
> ATOM 28 HB2 TYD 3 6.640 -87.531 -50.786 1.00 0.00
> ATOM 29 HB3 TYD 3 7.838 -86.443 -50.096 1.00 0.00
> ATOM 30 CG TYD 3 7.737 -86.385 -52.220 1.00 0.00
> ATOM 31 CD1 TYD 3 7.471 -87.036 -53.437 1.00 0.00
> ATOM 32 HD1 TYD 3 7.116 -88.054 -53.458 1.00 0.00
> ATOM 33 CE1 TYD 3 7.626 -86.356 -54.649 1.00 0.00
> ATOM 34 HE1 TYD 3 7.408 -86.843 -55.581 1.00 0.00
> ATOM 35 CZ TYD 3 8.074 -85.029 -54.653 1.00 0.00
> ATOM 36 OH TYD 3 8.301 -84.438 -55.844 1.00 0.00
> ATOM 38 CE2 TYD 3 8.305 -84.351 -53.441 1.00 0.00
> ATOM 39 HE2 TYD 3 8.628 -83.325 -53.458 1.00 0.00
> ATOM 40 CD2 TYD 3 8.135 -85.035 -52.221 1.00 0.00
> ATOM 41 HD2 TYD 3 8.340 -84.539 -51.286 1.00 0.00
> ATOM 42 C TYD 3 8.757 -88.702 -49.364 1.00 0.00
> ATOM 43 O TYD 3 8.005 -89.556 -48.894 1.00 0.00
> ATOM 44 N SER 4 9.675 -88.075 -48.649 1.00 0.00
> ATOM 45 H SER 4 10.274 -87.385 -49.078 1.00 0.00
> ATOM 46 CA SER 4 9.734 -88.242 -47.215 1.00 0.00
> ATOM 47 HA SER 4 8.799 -88.662 -46.842 1.00 0.00
> ATOM 48 CB SER 4 10.872 -89.179 -46.813 1.00 0.00
> ATOM 49 HB2 SER 4 10.664 -89.585 -45.822 1.00 0.00
> ATOM 50 HB3 SER 4 10.943 -90.005 -47.522 1.00 0.00
> ATOM 51 OG SER 4 12.097 -88.479 -46.758 1.00 0.00
> ATOM 52 HG SER 4 12.758 -89.008 -47.219 1.00 0.00
> ATOM 53 C SER 4 9.921 -86.870 -46.586 1.00 0.00
> ATOM 54 O SER 4 10.463 -85.956 -47.209 1.00 0.00
> ATOM 55 N NME 5 9.454 -86.732 -45.354 1.00 0.00
> ATOM 56 H NME 5 9.007 -87.512 -44.893 1.00 0.00
> ATOM 57 C NME 5 9.562 -85.482 -44.630 1.00 0.00
> ATOM 58 H1 NME 5 10.063 -84.742 -45.254 1.00 0.00
> ATOM 59 H2 NME 5 8.565 -85.123 -44.372 1.00 0.00
> ATOM 60 H3 NME 5 10.138 -85.638 -43.718 1.00 0.00
> TER
> END
> ----------------------------------------------------------------------------------------
>
> From: Todd Minehardt <todd.minehardt.gmail.com>
> Sent: Thursday, November 2, 2023 3:11 PM
> To: Xiangwei Zhu <xzhu.sutrobio.com>; AMBER Mailing List <amber.ambermd.org>
> Subject: Re: [AMBER] Model a protein with Tyrosine anion
>
> 1. Save your PDB file as TYD.pdb (I'm making up the name TYrosine Deprotonated), and I am assuming you want the hydrogen on the OH in the ring removed;
> 2. Remove the line with the atom type 'HH" (line 15 in your file, above);
>
> It will look like:
>
> ATOM 3371 N TYD 214 1.720 -90.946 -37.554 -0.41 0.00 N
> ATOM 3372 H TYD 214 1.540 -90.149 -38.148 0.27 0.00 H
> ATOM 3373 CA TYD 214 3.000 -91.015 -36.877 -0.00 0.00 C
> ATOM 3374 HA TYD 214 3.441 -92.000 -37.040 0.08 0.00 H
> ATOM 3375 CB TYD 214 3.946 -89.962 -37.446 -0.01 0.00 C
> ATOM 3376 HB2 TYD 214 4.088 -90.161 -38.509 0.02 0.00 H
> ATOM 3377 HB3 TYD 214 3.508 -88.971 -37.358 0.02 0.00 H
> ATOM 3378 CG TYD 214 5.285 -89.953 -36.769 -0.00 0.00 C
> ATOM 3379 CD1 TYD 214 5.506 -89.174 -35.638 -0.19 0.00 C
> ATOM 3380 HD1 TYD 214 4.709 -88.560 -35.242 0.16 0.00 H
> ATOM 3381 CE1 TYD 214 6.726 -89.173 -35.006 -0.23 0.00 C
> ATOM 3382 HE1 TYD 214 6.883 -88.567 -34.126 0.16 0.00 H
> ATOM 3383 CZ TYD 214 7.751 -89.956 -35.506 0.32 0.00 C
> ATOM 3384 OH TYD 214 8.969 -89.949 -34.874 -0.55 0.00 O
> ATOM 3386 CE2 TYD 214 7.562 -90.739 -36.631 -0.23 0.00 C
> ATOM 3387 HE2 TYD 214 8.366 -91.353 -37.013 0.16 0.00 H
> ATOM 3388 CD2 TYD 214 6.331 -90.736 -37.253 -0.19 0.00 C
> ATOM 3389 HD2 TYD 214 6.182 -91.356 -38.124 0.16 0.00 H
> ATOM 3390 C TYD 214 2.814 -90.809 -35.372 0.59 0.00 C
> ATOM 3391 O TYD 214 3.416 -91.509 -34.552 -0.56 0.00 O
>
> 3. Create the prepi file:
> antechamber -fi pdb -i TYD.pdb -fo prepi -o TYD.prepi -seq y -rn TYD -nc -1 -c bcc -j 5
>
> 4. Create the frcmod file:
> parmchk2 -i TYD.prepi -f prepi -o TYD.frcmod
>
> 5. Copy your file TYD.pdb to test.pdb and remove several of the atoms randomly (say, 10 of them);
>
> It will look like:
>
> ATOM 3371 N TYD 214 1.720 -90.946 -37.554 -0.41 0.00 N
> ATOM 3373 CA TYD 214 3.000 -91.015 -36.877 -0.00 0.00 C
> ATOM 3375 CB TYD 214 3.946 -89.962 -37.446 -0.01 0.00 C
> ATOM 3378 CG TYD 214 5.285 -89.953 -36.769 -0.00 0.00 C
> ATOM 3379 CD1 TYD 214 5.506 -89.174 -35.638 -0.19 0.00 C
> ATOM 3381 CE1 TYD 214 6.726 -89.173 -35.006 -0.23 0.00 C
> ATOM 3386 CE2 TYD 214 7.562 -90.739 -36.631 -0.23 0.00 C
> ATOM 3387 HE2 TYD 214 8.366 -91.353 -37.013 0.16 0.00 H
> ATOM 3388 CD2 TYD 214 6.331 -90.736 -37.253 -0.19 0.00 C
> ATOM 3389 HD2 TYD 214 6.182 -91.356 -38.124 0.16 0.00 H
> ATOM 3390 C TYD 214 2.814 -90.809 -35.372 0.59 0.00 C
> ATOM 3391 O TYD 214 3.416 -91.509 -34.552 -0.56 0.00 O
> 6. Using vi - and only vi - create a file called tleap.in<http://tleap.in>, in which you will have:
>
> source leaprc.protein.ff19SB
> source leaprc.gaff
> loadamberprep TYD.prepi
> loadamberparams TYD.frcmod
> mol = loadpdb test.pdb
> saveamberparm mol TYD.prmtop TYD.crd
>
> 7. tleap -s -f tleap.in<http://tleap.in>
>
> 8. We are doing steps 5 through 8 to make sure the prepi and frcmod files recreate the desired molecole (tyrosine minus the -OH group hydrogen):
>
> ambpdb -p TYD.prmtop -c TYD.crd > test_check.pdb
> 9. Look at test_check.pdb in a viewer (Chimerax, pymol, Avogodro2, etc.) and make sure it looks ok.
>
> 10. In your system of interest, you will replace each occurrence of the new tyrosine with the symbol TYD and load the parameters as in step 6.
>
> 11. You are still not off the hook, since the process doesn't always produce the correct atom types (like aromatic carbons), so you might need to manually go into the prepi file and change things to reflect the proper chemistry.
>
> 12. In case you want to cut straight to the chase - and I have not checked that the prepi file is correct (but hey, it does produce the thing you want):
>
> TYD.prepi:
>
> -----------------------------------------------------------------------------------------------------------
> 0 0 2
>
> This is a remark line
> molecule.res
> TYD INT 0
> CORRECT OMIT DU BEG
> 0.0000
> 1 DUMM DU M 0 -1 -2 0.000 .0 .0 .00000
> 2 DUMM DU M 1 0 -1 1.449 .0 .0 .00000
> 3 DUMM DU M 2 1 0 1.523 111.21 .0 .00000
> 4 O o M 3 2 1 1.540 111.208 -180.000 -0.459000
> 5 C c1 M 4 3 2 1.235 60.822 130.486 -0.023000
> 6 CA c3 M 5 4 3 1.530 121.164 -120.024 -0.047000
> 7 N n2 S 6 5 4 1.450 110.215 137.156 -0.272000
> 8 H hn E 7 6 5 1.010 118.002 110.354 0.116000
> 9 HA h1 E 6 5 4 1.091 108.509 17.547 0.147000
> 10 CB c3 M 6 5 4 1.526 110.441 -101.213 -0.118000
> 11 HB2 hc E 10 6 5 1.091 108.559 177.756 0.079500
> 12 HB3 hc E 10 6 5 1.087 110.438 -64.844 0.079500
> 13 CG ca M 10 6 5 1.500 112.906 56.850 -0.212000
> 14 CD1 ca M 13 10 6 1.391 120.798 -88.734 -0.084000
> 15 HD1 ha E 14 13 10 1.081 119.915 -0.460 0.096500
> 16 CE1 ca M 14 13 10 1.374 121.030 179.305 -0.244000
> 17 HE1 ha E 16 14 13 1.080 120.285 -179.719 0.142500
> 18 CZ ca M 16 14 13 1.383 119.422 0.218 0.226000
> 19 OH o E 18 16 14 1.372 119.230 179.810 -0.342000
> 20 CE2 ca M 18 16 14 1.384 120.862 -0.072 -0.244000
> 21 HE2 ha E 20 18 16 1.081 120.463 -179.646 0.142500
> 22 CD2 ca M 20 18 16 1.379 119.168 -0.215 -0.084000
> 23 HD2 ha E 22 20 18 1.079 119.067 -179.316 0.096500
>
>
> LOOP
> CD2 CG
>
> IMPROPER
> CB CD1 CG CD2
> CG CE1 CD1 HD1
> CD1 CZ CE1 HE1
> CE1 CE2 CZ OH
> CZ CD2 CE2 HE2
> CG CE2 CD2 HD2
>
> DONE
> STOP
>
> -----------------------------------------------------------------------------------------------------------
>
> TYD.frcmod:
>
> -----------------------------------------------------------------------------------------------------------
> Remark line goes here
> MASS
>
> BOND
>
> ANGLE
> c3-c1-o 57.930 180.000 Calculated with empirical approach for c3-c1-o
> c1-c3-n2 68.008 109.895 Calculated with empirical approach for c1-c3-n2
>
> DIHE
>
> IMPROPER
> ca-ca-ca-ha 1.1 180.0 2.0 Using general improper torsional angle X- X-ca-ha, penalty score= 6.0)
> ca-ca-ca-o 1.1 180.0 2.0 Using the default value
>
> NONBON
> -----------------------------------------------------------------------------------------------------------
>
> Cheers,
>
> Todd
>
> On Thu, Nov 2, 2023 at 3:35 PM Xiangwei Zhu via AMBER <amber.ambermd.org<mailto:amber.ambermd.org>> wrote:
> Hi All,
> I'm working on a protein that needs to have one of its tyrosine deprotonated. The coordinate is shown below. A few questions on it:
> 1. Is there a best of practice to do the modification in tleap?
> 2. How to change it manually?
> 3. How to load the correct force field for tyrosine anion?
> Thanks a lot!
> Xiangwei
>
> Below is the coordinate:
> --------------------------------
>
> ATOM 3371 N TYR 214 1.720 -90.946 -37.554 -0.41 0.00 N
> ATOM 3372 H TYR 214 1.540 -90.149 -38.148 0.27 0.00 H
> ATOM 3373 CA TYR 214 3.000 -91.015 -36.877 -0.00 0.00 C
> ATOM 3374 HA TYR 214 3.441 -92.000 -37.040 0.08 0.00 H
> ATOM 3375 CB TYR 214 3.946 -89.962 -37.446 -0.01 0.00 C
> ATOM 3376 HB2 TYR 214 4.088 -90.161 -38.509 0.02 0.00 H
> ATOM 3377 HB3 TYR 214 3.508 -88.971 -37.358 0.02 0.00 H
> ATOM 3378 CG TYR 214 5.285 -89.953 -36.769 -0.00 0.00 C
> ATOM 3379 CD1 TYR 214 5.506 -89.174 -35.638 -0.19 0.00 C
> ATOM 3380 HD1 TYR 214 4.709 -88.560 -35.242 0.16 0.00 H
> ATOM 3381 CE1 TYR 214 6.726 -89.173 -35.006 -0.23 0.00 C
> ATOM 3382 HE1 TYR 214 6.883 -88.567 -34.126 0.16 0.00 H
> ATOM 3383 CZ TYR 214 7.751 -89.956 -35.506 0.32 0.00 C
> ATOM 3384 OH TYR 214 8.969 -89.949 -34.874 -0.55 0.00 O
> ATOM 3385 HH TYR 214 9.571 -90.629 -35.191 0.39 0.00 H
> ATOM 3386 CE2 TYR 214 7.562 -90.739 -36.631 -0.23 0.00 C
> ATOM 3387 HE2 TYR 214 8.366 -91.353 -37.013 0.16 0.00 H
> ATOM 3388 CD2 TYR 214 6.331 -90.736 -37.253 -0.19 0.00 C
> ATOM 3389 HD2 TYR 214 6.182 -91.356 -38.124 0.16 0.00 H
> ATOM 3390 C TYR 214 2.814 -90.809 -35.372 0.59 0.00 C
> ATOM 3391 O TYR 214 3.416 -91.509 -34.552 -0.56 0.00 O
>
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Received on Fri Nov 03 2023 - 04:30:02 PDT
