No default type errors -NH2 and COO- amino acid termini patches for pH 10 simulations

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1

GROMACS version:2022
GROMACS modification: No
Much thanks for any help and guidance on these errors - I am studying mixtures of amino acids at pH 10; at this pH the N-term is neutral NH2 and the C-term is negative COO-. I am using the charmm27 force field to parametrize and patch each amino acid. However I’m getting errors that I thought would taken care of with the C and N term nbd files. These are the errors I’m getting along with snippets of my topology files. Thanks again for your time and effort reading this.

ERROR 1 [file phe.top, line 136]:
No default U-B types
-------------------------------My input to this post--------------
Topology file line 136: (1 4 20. 5)
atoms: (1 NH2 2 PHE N)
(4 CT1 2 PHE CA)
(20 CC 2 PHE C)

The NH2 amino acids.n.tdb file is:
[ NH2 ]
[ replace ]
N NH2 14.007 -0.96
CA CT1 12.011 0.19
HA HB 1.008 0.09
[ add ]
2 4 HT N CA C
H 1.008 0.34 -1
[ delete ]
HN

This angle does not seem to be defined in the aminoacids.n.tdb file

  1. Is this a typo for an angle that was not inserted?
  2. Does a parametrization exist for this angle?

-------------My input to this post--------------

ERROR 2 [file phe.top, line 172]:
** No default Proper Dih. types**

2 1 4 20 9 (line 172)

2 H 2 PHE HT1
1 NH2 2 PHE N
4 CT1 2 PHE CA
20 CC 2 PHE C

From what I think this dihedral seems to be defined in the aminoacid.n.tdb file

  1. What am I missing?

end-------------My input to this post--------------

ERROR 3 [file phe.top, line 175]:
** No default Proper Dih. types**

start-------------My input to this post--------------
3 1 4 20 9 (line 175)

3 H 2 PHE HT2
1 NH2 2 PHE N
4 CT1 2 PHE CA
20 CC 2 PHE C

From what I think this dihedral seems to be defined in the aminoacid.n.tdb file

  1. What am I missing?

end-------------My input to this post--------------

2

I found what I think is the issue - the ffbonded.itp file in Charmm36-jul2021.ff switches the order of atoms in the angle and dihedral parameters of NH2-CT1-CC in the topology generated by pdb2gmx, however the in the ffbonded.itp the order is NH2-CC-CT1 - I changed the order to match the topology created by pdb2gmx and that solved the angle issue;

For the dihedral, the same issue happened with order - in the topology file created by pdb2gmx the order is H-NH2-CT1-CC; however H-NH2-CC-CT1 is the order in ffbonded.itp - I also changed the ffbonded.itp file to match the topology generated by pdb2gmx; additionally the H-NH2-CT2-CC was also switched in the ffbonded.itp file

3

Hi,

such reordering is only permitted if the mathematical form of the potential function is invariant to the change. What you do does indeed silence the error message, but you introduce unwanted (incorrect) behaviour.

The CHARMM parameter set you want to use was parametrized for proteins/peptides, i.e. polymers (oligomers) of amino-acids, where the effects resulting from the chain have been implicitly accounted for. The chemical/conformational behaviour of stand-alone monomers is expected to be different, therefore you should not blindly apply these parameters for your case. Accordingly, the parameters you need are not even available in the upstream force field data set.

I’d suggest to search for a compatible topology in the CGenFF part of the upstream CHARMM data, or attempt to parametrize the required molecules with CGenFF.

By the way, the interaction parameters you have found in the force field parameter set are originally for the amidated C-terminus (CT2 patch residue in the upstream CHARMM force field dataset). For example, the angle parameter NH2-CC-CT1 is good for the amidated C-terminus (CT2 in the upstream CHARMM force field), where it describes the angle term of Calpha - C(=O) - N(H2). You exchange two carbons with different chemical character: one with an =O attached and one carrying a -NH2 group. This is seldom correct.

Mixing/matching force field parameters is always a dangerous business. Any change to them requires serious (non-trivial) validation. If you are lucky, you only induce instability in your system (“blowing up”). If you are not, you get seemingly meaningful but completely invalid results (“garbage in, garbage out”).

Hope this helps.

Kind regards,

Andras

1 Like
4

Don’t use pdb2gmx - too complicated/too much editing.

Here is my deprotonated ALA, which should work with CHARMM36.
Generated with CGenFF (instead of including a .prm file, the parameters added here)

ALA.gro

Glycine aRginine prOline Methionine Alanine Cystine Serine
   12
    2ALA      N    1  -0.068  -0.123  -0.049
    2ALA    HT1    2  -0.167  -0.109  -0.049
    2ALA    HT2    3  -0.041  -0.174  -0.131
    2ALA     CA    4  -0.000   0.006  -0.049
    2ALA     HA    5  -0.022   0.054  -0.134
    2ALA     CB    6  -0.051   0.086   0.073
    2ALA    HB1    7  -0.006   0.175   0.075
    2ALA    HB2    8  -0.150   0.098   0.065
    2ALA    HB3    9  -0.030   0.035   0.156
    2ALA      C   10   0.150  -0.011  -0.049
    2ALA    OT1   11   0.205  -0.109   0.003
    2ALA    OT2   12   0.225   0.102  -0.049
   0.39189   0.34938   0.29080

ALA.itp

[ moleculetype ]
; Name            nrexcl
ALA            3

[ atoms ]
;   nr       type  resnr residue  atom   cgnr     charge       mass  typeB    chargeB      massB
; residue   2 ALA rtp ALA  q -1.0
     1        NH2      2    ALA      N      1      -0.96     14.007   ; qtot -0.96
     2          H      2    ALA    HT1      2       0.34      1.008   ; qtot -0.62
     3          H      2    ALA    HT2      3       0.34      1.008   ; qtot -0.28
     4        CT1      2    ALA     CA      4       0.19     12.011   ; qtot -0.09
     5         HB      2    ALA     HA      5       0.09      1.008   ; qtot 0
     6        CT3      2    ALA     CB      6      -0.27     12.011   ; qtot -0.27
     7         HA      2    ALA    HB1      7       0.09      1.008   ; qtot -0.18
     8         HA      2    ALA    HB2      8       0.09      1.008   ; qtot -0.09
     9         HA      2    ALA    HB3      9       0.09      1.008   ; qtot 0
    10         CC      2    ALA      C     10       0.34     12.011   ; qtot 0.34
    11         OC      2    ALA    OT1     11      -0.67     15.999   ; qtot -0.33
    12         OC      2    ALA    OT2     12      -0.67     15.999   ; qtot -1

[ bonds ]
;  ai    aj funct            c0            c1            c2            c3
    1     2     1 
    1     3     1 
    1     4     1 
    4     5     1 
    4     6     1 
    4    10     1 
    6     7     1 
    6     8     1 
    6     9     1 
   10    11     1 
   10    12     1 

[ pairs ]
;  ai    aj funct            c0            c1            c2            c3
    1     7     1 
    1     8     1 
    1     9     1 
    1    11     1 
    1    12     1 
    2     5     1 
    2     6     1 
    2    10     1 
    3     5     1 
    3     6     1 
    3    10     1 
    5     7     1 
    5     8     1 
    5     9     1 
    5    11     1 
    5    12     1 
    6    11     1 
    6    12     1 
    7    10     1 
    8    10     1 
    9    10     1 

[ angles ]
;  ai    aj    ak funct            c0            c1            c2            c3
    2     1     3     5 
    2     1     4     5 
    3     1     4     5 
    1     4     5     5 
    1     4     6     5 
    1     4    10     5  110.0000        365.6816        0.0     0.0 ;NH3 CT1 CC
    5     4     6     5 
    5     4    10     5 
    6     4    10     5 
    4     6     7     5 
    4     6     8     5 
    4     6     9     5 
    7     6     8     5 
    7     6     9     5 
    8     6     9     5 
    4    10    11     5 
    4    10    12     5 
   11    10    12     5 

[ dihedrals ]
;  ai    aj    ak    al funct            c0            c1            c2            c3            c4            c5
    2     1     4     5     9 
    2     1     4     6     9 
    2     1     4    10     9 0.00    0.4184  3; X    CT1     NH3     X
    3     1     4     5     9 
    3     1     4     6     9 
    3     1     4    10     9 0.00    0.4184  3; X    CT1     NH3     X
    1     4     6     7     9 
    1     4     6     8     9 
    1     4     6     9     9 
    5     4     6     7     9 
    5     4     6     8     9 
    5     4     6     9     9 
   10     4     6     7     9 
   10     4     6     8     9 
   10     4     6     9     9 
    1     4    10    11     9 
    1     4    10    12     9 
    5     4    10    11     9 
    5     4    10    12     9 
    6     4    10    11     9 
    6     4    10    12     9 

[ dihedrals ]
;  ai    aj    ak    al funct            c0            c1            c2            c3
   10     4    12    11     2

Hope this helps:)

BW,
V