How to solve the "No default Proper Dih. types?"

I need more information. You should have gotten a lig.prm file (which is just a GROMACS topology) that you need to #include in the system topology to provide these parameters. If you need further help, I will need access to all the relevant files related to your ligand.

Thank you sir for your response. I used gromos forcefield so no
lig.prm file wasn’t generated

Yes. We got a lig.prm file and it was #included in the topol.top file. Despite this, the above mention error was occurred.

The ligand we employed was Pixantrone. We drew this structure, minimized it and then docked it in out target protein.
An analog of this ligand can be found in the pdb 4G0W.

I am unable to upload the ligand files. It says that new users can not upload documents and I joined this forum today itself! Hence, I shall paste the content of those files here itself.

LIG.mol2

@<TRIPOS>MOLECULE
LIG
    43    45     1
SMALL       
USER_CHARGES
****        
gtpase kras; chain: a; synonym: k-ras 2,ki-ras,c-k-ras,c-ki-ras; engineered: yes
@<TRIPOS>ATOM
    1 H91     7.7930   -3.1192   62.9906 H      1 LIG1       0.1500
    2 C9      7.8087   -4.0433   62.4242 C.ar   1 LIG1      -0.1500
    3 C10     6.6293   -4.7505   62.3423 C.ar   1 LIG1      -0.1500
    4 H101    5.7678   -4.3354   62.8521 H      1 LIG1       0.1500
    5 C7      6.5338   -5.9411   61.6386 C.ar   1 LIG1       0.1000
    6 N2      5.3010   -6.6409   61.5592 N.pl3   1 LIG1      -0.8690
    7 H21     5.3192   -7.5493   61.0935 H      1 LIG1       0.4000
    8 C15     4.0237   -6.1762   62.1229 C.3    1 LIG1       0.3690
    9 H151    3.8939   -5.0973   61.9870 H      1 LIG1       0.0000
   10 H152    3.2193   -6.6413   61.5447 H      1 LIG1       0.0000
   11 C17     3.8736   -6.5912   63.5924 C.3    1 LIG1       0.2700
   12 H171    4.6596   -6.1445   64.2086 H      1 LIG1       0.0000
   13 H172    3.9921   -7.6769   63.6743 H      1 LIG1       0.0000
   14 N4      2.5639   -6.2221   64.1353 N.3    1 LIG1      -0.9900
   15 H41     2.4577   -6.6159   65.0700 H      1 LIG1       0.3600
   16 H42     2.4917   -5.2108   64.2652 H      1 LIG1       0.3600
   17 C1      7.7002   -6.3956   60.9927 C.ar   1 LIG1       0.0860
   18 C2      8.9082   -5.6872   61.1019 C.ar   1 LIG1       0.0860
   19 C8      8.9765   -4.4812   61.8191 C.ar   1 LIG1       0.1000
   20 N3     10.1738   -3.7209   61.8975 N.pl3   1 LIG1      -0.8690
   21 H31    11.0225   -4.1407   61.5139 H      1 LIG1       0.4000
   22 C14    10.2571   -2.3301   62.3616 C.3    1 LIG1       0.3690
   23 H141    9.7075   -2.1856   63.2971 H      1 LIG1       0.0000
   24 H142   11.3055   -2.1195   62.5967 H      1 LIG1       0.0000
   25 C16     9.7871   -1.3637   61.2695 C.3    1 LIG1       0.2700
   26 H161    8.7538   -1.5816   60.9889 H      1 LIG1       0.0000
   27 H162   10.3909   -1.5073   60.3677 H      1 LIG1       0.0000
   28 N5      9.8936    0.0332   61.6925 N.3    1 LIG1      -0.9900
   29 H51     9.2225    0.2326   62.4380 H      1 LIG1       0.3600
   30 H52     9.6396    0.6456   60.9184 H      1 LIG1       0.3600
   31 C4     10.1364   -6.2108   60.4346 C.2    1 LIG1       0.3980
   32 O2     11.2530   -5.7654   60.6707 O.2    1 LIG1      -0.5700
   33 C6     10.0141   -7.2971   59.4490 C.ar   1 LIG1       0.0860
   34 C12    11.0881   -7.6594   58.6443 C.ar   1 LIG1      -0.1500
   35 H121   12.0562   -7.1731   58.7178 H      1 LIG1       0.1500
   36 C13    10.8897   -8.6631   57.7156 C.ar   1 LIG1       0.1600
   37 H131   11.7004   -8.9710   57.0655 H      1 LIG1       0.1500
   38 N1      9.7291   -9.3166   57.5349 N.ar   1 LIG1      -0.6200
   39 C11     8.7269   -8.9666   58.3545 C.ar   1 LIG1       0.1600
   40 H111    7.8133   -9.5269   58.2104 H      1 LIG1       0.1500
   41 C5      8.8179   -7.9675   59.3109 C.ar   1 LIG1       0.0860
   42 C3      7.6606   -7.6316   60.1569 C.2    1 LIG1       0.3980
   43 O1      6.6912   -8.3797   60.1344 O.2    1 LIG1      -0.5700
@<TRIPOS>BOND
    1     1     2 1 
    2     2     3 2 
    3     2    19 1 
    4     3     4 1 
    5     3     5 1 
    6     5     6 1 
    7     5    17 2 
    8     6     7 1 
    9     6     8 1 
   10     8     9 1 
   11     8    10 1 
   12     8    11 1 
   13    11    12 1 
   14    11    13 1 
   15    11    14 1 
   16    14    15 1 
   17    14    16 1 
   18    17    18 1 
   19    17    42 1 
   20    18    19 2 
   21    18    31 1 
   22    19    20 1 
   23    20    21 1 
   24    20    22 1 
   25    22    23 1 
   26    22    24 1 
   27    22    25 1 
   28    25    26 1 
   29    25    27 1 
   30    25    28 1 
   31    28    29 1 
   32    28    30 1 
   33    31    32 2 
   34    31    33 1 
   35    33    34 1 
   36    33    41 2 
   37    34    35 1 
   38    34    36 2 
   39    36    37 1 
   40    36    38 1 
   41    38    39 2 
   42    39    40 1 
   43    39    41 1 
   44    41    42 1 
   45    42    43 2 
@<TRIPOS>SUBSTRUCTURE
    1   LIG1         1
@<TRIPOS>CRYSIN
   90.1590   90.1590   90.1590   90.0000   90.0000   90.0000     0     0

LIG.str

* Toppar stream file generated by
* CHARMM General Force Field (CGenFF) program version 2.5
* For use with CGenFF version 4.5
*

read rtf card append
* Topologies generated by
* CHARMM General Force Field (CGenFF) program version 2.5
*
36 1

! "penalty" is the highest penalty score of the associated parameters.
! Penalties lower than 10 indicate the analogy is fair; penalties between 10
! and 50 mean some basic validation is recommended; penalties higher than
! 50 indicate poor analogy and mandate extensive validation/optimization.

RESI LIG            0.000 ! param penalty=  45.000 ; charge penalty=  30.477
GROUP            ! CHARGE   CH_PENALTY
ATOM H91    HGR61   0.115 !    0.000
ATOM C9     CG2R61 -0.112 !    0.000
ATOM C10    CG2R61 -0.112 !    0.000
ATOM H101   HGR61   0.115 !    0.000
ATOM C7     CG2R61 -0.020 !   16.260
ATOM N2     NG311  -0.553 !   25.251
ATOM H21    HGPAM1  0.371 !    0.000
ATOM C15    CG321  -0.011 !   14.138
ATOM H151   HGA2    0.090 !    0.000
ATOM H152   HGA2    0.090 !    0.000
ATOM C17    CG321   0.083 !   17.378
ATOM H171   HGA2    0.090 !    0.000
ATOM H172   HGA2    0.090 !    0.000
ATOM N4     NG321  -0.877 !   12.523
ATOM H41    HGPAM2  0.319 !    0.000
ATOM H42    HGPAM2  0.319 !    0.000
ATOM C1     CG2R61  0.020 !   26.841
ATOM C2     CG2R61  0.020 !   26.841
ATOM C8     CG2R61 -0.020 !   16.260
ATOM N3     NG311  -0.553 !   25.251
ATOM H31    HGPAM1  0.371 !    0.000
ATOM C14    CG321  -0.011 !   14.138
ATOM H141   HGA2    0.090 !    0.000
ATOM H142   HGA2    0.090 !    0.000
ATOM C16    CG321   0.083 !   17.378
ATOM H161   HGA2    0.090 !    0.000
ATOM H162   HGA2    0.090 !    0.000
ATOM N5     NG321  -0.877 !   12.523
ATOM H51    HGPAM2  0.319 !    0.000
ATOM H52    HGPAM2  0.319 !    0.000
ATOM C4     CG2O5   0.424 !   30.477
ATOM O2     OG2D3  -0.459 !    0.000
ATOM C6     CG2R61  0.015 !   21.571
ATOM C12    CG2R61 -0.114 !    1.700
ATOM H121   HGR61   0.115 !    0.000
ATOM C13    CG2R61  0.182 !    0.000
ATOM H131   HGR62   0.122 !    0.000
ATOM N1     NG2R60 -0.603 !    0.000
ATOM C11    CG2R61  0.181 !    1.700
ATOM H111   HGR62   0.120 !    0.000
ATOM C5     CG2R61  0.022 !   21.571
ATOM C3     CG2O5   0.426 !   30.477
ATOM O1     OG2D3  -0.459 !    0.000

BOND H91  C9  
BOND C9   C10 
BOND C9   C8  
BOND C10  H101
BOND C10  C7  
BOND C7   N2  
BOND C7   C1  
BOND N2   H21 
BOND N2   C15 
BOND C15  H151
BOND C15  H152
BOND C15  C17 
BOND C17  H171
BOND C17  H172
BOND C17  N4  
BOND N4   H41 
BOND N4   H42 
BOND C1   C2  
BOND C1   C3  
BOND C2   C8  
BOND C2   C4  
BOND C8   N3  
BOND N3   H31 
BOND N3   C14 
BOND C14  H141
BOND C14  H142
BOND C14  C16 
BOND C16  H161
BOND C16  H162
BOND C16  N5  
BOND N5   H51 
BOND N5   H52 
BOND C4   O2  
BOND C4   C6  
BOND C6   C12 
BOND C6   C5  
BOND C12  H121
BOND C12  C13 
BOND C13  H131
BOND C13  N1  
BOND N1   C11 
BOND C11  H111
BOND C11  C5  
BOND C5   C3  
BOND C3   O1  
IMPR C4     C2     C6     O2    
IMPR C3     C1     C5     O1    

END

read param card flex append
* Parameters generated by analogy by
* CHARMM General Force Field (CGenFF) program version 2.5
*

! Penalties lower than 10 indicate the analogy is fair; penalties between 10
! and 50 mean some basic validation is recommended; penalties higher than
! 50 indicate poor analogy and mandate extensive validation/optimization.

BONDS

ANGLES
CG2R61 CG2O5  CG2R61   40.00    117.20 ! LIG , from CG2O3 CG2O5 CG2R61, penalty= 34

DIHEDRALS
CG2R61 CG2O5  CG2R61 CG2R61     1.5850  2   180.00 ! LIG , from CG2O3 CG2O5 CG2R61 CG2R61, penalty= 34
CG2O5  CG2R61 CG2R61 CG2O5      3.1000  2   180.00 ! LIG , from CG2O5 CG2R61 CG2R61 CG2R61, penalty= 45
CG2O5  CG2R61 CG2R61 NG311      3.1000  2   180.00 ! LIG , from CG2R61 CG2R61 CG2R61 NG311, penalty= 45
NG311  CG321  CG321  NG321      0.3000  3     0.00 ! LIG , from CG321 CG321 CG321 NG311, penalty= 39
CG321  CG321  NG311  CG2R61     0.8000  1   180.00 ! LIG , from CG321 CG321 NG311 CG2R64, penalty= 4
CG321  CG321  NG311  CG2R61     1.1000  3     0.00 ! LIG , from CG321 CG321 NG311 CG2R64, penalty= 4

IMPROPERS
CG2O5  CG2R61 CG2R61 OG2D3     72.0000  0     0.00 ! LIG , from CG2O5 CG2O3 CG2R61 OG2D3, penalty= 19

END
RETURN

LIG.gro

GROningen MAchine for Chemical Simulation
   43
    1LIG    H91    1   0.779  -0.312   6.299
    1LIG     C9    2   0.781  -0.404   6.242
    1LIG    C10    3   0.663  -0.475   6.234
    1LIG   H101    4   0.577  -0.433   6.285
    1LIG     C7    5   0.653  -0.594   6.164
    1LIG     N2    6   0.530  -0.664   6.156
    1LIG    H21    7   0.532  -0.755   6.109
    1LIG    C15    8   0.402  -0.618   6.212
    1LIG   H151    9   0.389  -0.510   6.199
    1LIG   H152   10   0.322  -0.664   6.155
    1LIG    C17   11   0.387  -0.659   6.359
    1LIG   H171   12   0.466  -0.614   6.421
    1LIG   H172   13   0.399  -0.768   6.367
    1LIG     N4   14   0.256  -0.622   6.413
    1LIG    H41   15   0.246  -0.662   6.507
    1LIG    H42   16   0.249  -0.521   6.426
    1LIG     C1   17   0.770  -0.640   6.099
    1LIG     C2   18   0.891  -0.569   6.110
    1LIG     C8   19   0.898  -0.448   6.182
    1LIG     N3   20   1.017  -0.372   6.190
    1LIG    H31   21   1.102  -0.414   6.151
    1LIG    C14   22   1.026  -0.233   6.236
    1LIG   H141   23   0.971  -0.219   6.330
    1LIG   H142   24   1.131  -0.212   6.260
    1LIG    C16   25   0.979  -0.136   6.127
    1LIG   H161   26   0.875  -0.158   6.099
    1LIG   H162   27   1.039  -0.151   6.037
    1LIG     N5   28   0.989   0.003   6.169
    1LIG    H51   29   0.922   0.023   6.244
    1LIG    H52   30   0.964   0.065   6.092
    1LIG     C4   31   1.014  -0.621   6.043
    1LIG     O2   32   1.125  -0.576   6.067
    1LIG     C6   33   1.001  -0.730   5.945
    1LIG    C12   34   1.109  -0.766   5.864
    1LIG   H121   35   1.206  -0.717   5.872
    1LIG    C13   36   1.089  -0.866   5.772
    1LIG   H131   37   1.170  -0.897   5.707
    1LIG     N1   38   0.973  -0.932   5.753
    1LIG    C11   39   0.873  -0.897   5.835
    1LIG   H111   40   0.781  -0.953   5.821
    1LIG     C5   41   0.882  -0.797   5.931
    1LIG     C3   42   0.766  -0.763   6.016
    1LIG     O1   43   0.669  -0.838   6.013
   0.00000   0.00000   0.00000

LIG.prm


[ bondtypes ]
;      i        j  func           b0           kb


[ angletypes ]
;      i        j        k  func       theta0       ktheta          ub0          kub
  CG2R61    CG2O5   CG2R61     5   117.200000   334.720000   0.00000000         0.00


[ dihedraltypes ]
;      i        j        k        l  func         phi0         kphi  mult
  CG2R61    CG2O5   CG2R61   CG2R61     9   180.000000     6.631640     2
   CG2O5   CG2R61   CG2R61    CG2O5     9   180.000000    12.970400     2
   CG2O5   CG2R61   CG2R61    NG311     9   180.000000    12.970400     2
   NG311    CG321    CG321    NG321     9     0.000000     1.255200     3
   CG321    CG321    NG311   CG2R61     9   180.000000     3.347200     1
   CG321    CG321    NG311   CG2R61     9     0.000000     4.602400     3


[ dihedraltypes ]
; 'improper' dihedrals 
;      i        j        k        l  func         phi0         kphi
   CG2O5   CG2R61   CG2R61    OG2D3     2     0.000000   602.496000

Thank you very much for your response.

Regards
Hemant

Sorry, my response was to @heman_t but in your case you should revisit how you generated the ligand parameters. Did you use some server to generate it? Did you do it by hand?

Yes. We got a lig.prm file which was then #included in the topol.top file.

I’m unable to upload the relevant ligand files as it says that new users can not upload files.


[ bondtypes ]
;      i        j  func           b0           kb


[ angletypes ]
;      i        j        k  func       theta0       ktheta          ub0          kub
  CG2R61    CG2O5   CG2R61     5   117.200000   334.720000   0.00000000         0.00


[ dihedraltypes ]
;      i        j        k        l  func         phi0         kphi  mult
  CG2R61    CG2O5   CG2R61   CG2R61     9   180.000000     6.631640     2
   CG2O5   CG2R61   CG2R61    CG2O5     9   180.000000    12.970400     2
   CG2O5   CG2R61   CG2R61    NG311     9   180.000000    12.970400     2
   NG311    CG321    CG321    NG321     9     0.000000     1.255200     3
   CG321    CG321    NG311   CG2R61     9   180.000000     3.347200     1
   CG321    CG321    NG311   CG2R61     9     0.000000     4.602400     3


[ dihedraltypes ]
; 'improper' dihedrals 
;      i        j        k        l  func         phi0         kphi
   CG2O5   CG2R61   CG2R61    OG2D3     2     0.000000   602.496000

This is the prm file contents. The ligand is Pixantrone.
We drew the structure and then found its 3D structure by minimising its energy in ICM(molsoft).
Then we docked it in a protein.

@heman_t what dihedral does grompp say is missing (atom types, please).

@jalemkul

This is what I get :

@heman_t I need the actual atom types. Screenshots referring to line numbers (which mean nothing to me, or anyone else) are not helpful. It may be useful to upload all your files (at least the .top, ligand .itp and .prm files) somewhere that we can access them to look.

@jalemkul Apologies. I have uploaded the .itp and .prm files in an earlier message (Nov 18) in this discussion. You may have missed it because it was not delivered right away (it was stopped for scrutiny by this forum keepers). I can not upload the .top file (at least not whole of it) as it contains the protein information as well and I am not at liberty to share that.

Please let me know if anything else is needed.

@heman_t I see the original .str file but not the .itp. Please upload the lig.prm and lig.itp to somewhere like Google Drive rather than trying to attach or embed them here.

As for the system topology, that’s a rather important part of all this. At minimum, please paste the first non-blank lines before and after your #include statement for lig.prm. The parts related to the protein are rather unimportant in this context, but the location of the #include statement is key.

@jalemkul Thank you for the response, Justin.
Here is the link to the google drive folder.

Sorry. The link had restricted access earlier. Now anyone with that link can open it.

@heman_t the missing interactions are part of the latest CHARMM force field, which includes CGenFF 4.6. You’re likely using an outdated version of the CHARMM36 port. Get the July 2021 release and this should work.

Thank you for your response @jalemkul
Yes, I was using the feb-2021 version. However, despite using the newer version(jul-2021), there is not much progress.

When I include the lig.prm file, I get the following error in the ionization step:

ERROR 1 [file lig.prm, line 13]:

Encountered a second block of parameters for dihedral type 9 for the same atoms, 
with either different parameters and/or the first block has multiple lines. 
This is not supported.

line 13 is where the [ dihedraltypes ] starts.

Interpreting this error message as the lig.prm file being redundant, I tried without including it in the topol.top. This lead to the No default Proper Dih. types error.

Which version of CGenFF was used when your topology was generated? It will say within the original lig.str file.

Simply removing lig.prm is not a valid solution. You need to identify which specific block of parameters is at odds with the existing force field and remove those lines, not the entire topology. There are still parameters within lig.prm that your ligand requires.

CGenFF v4.5 was used for generating the parameters while that in the force field is v4.6

It did prompt in the beginning that this might lead to some problems. I continued hoping for the best.

Okay, I’ll try removing only those dihedral quadruplets which have already been defined in the ffbonded.itp

Yes, that is the problem you will run into when using different versions. The parameters that were previously unknown to the force field in version 4.5 have, in some cases, been determined and optimized for inclusion in 4.6, which is what you’re running into here. Your ligand prompted generation of “new” parameters that are no longer new.

@jalemkul After removing only those quadruplets from the lig.prm which have also been defined in the ffbonded.itp, I could move past this hurdle.

But another anomaly creeped in during the energy minimization step. I had faced this earlier too while using the Jul-2021 version of charmm36.

@Mikel led me to another similar issue. I tried reducing the em_step size, increase the box dimensions but in vain. I’m still trying out other ways to work around this issue.

@jalemkul There’s another system for which I was trying to run a MD simulation yesterday. I faced the same error as before…non-convergence of Fmax in the energy minimization step. I have faced the same error every time I tried to use the Jul2021 version of the charmm36 force field.

Here is the em.mdp file I used.

title		    = Minimization	; Title of run

; Parameters describing what to do, when to stop and what to save
integrator	    = steep		; Algorithm (steep = steepest descent minimization)
emtol		    = 1000.0  	; Stop minimization when the maximum force < 10.0 kJ/mol
emstep          = 0.01      ; Energy step size
nsteps		    = 50000	  	; Maximum number of (minimization) steps to perform

; Parameters describing how to find the neighbors of each atom and how to calculate the interactions
nstlist		    = 1		        ; Frequency to update the neighbor list and long range forces
cutoff-scheme   = Verlet
ns_type		    = grid		    ; Method to determine neighbor list (simple, grid)
rlist		    = 1.2		    ; Cut-off for making neighbor list (short range forces)
coulombtype	    = PME		    ; Treatment of long range electrostatic interactions
rcoulomb	    = 1.2		    ; long range electrostatic cut-off
vdwtype         = cutoff
vdw-modifier    = force-switch
rvdw-switch     = 1.0
rvdw		    = 1.2		    ; long range Van der Waals cut-off
pbc             = xyz 		    ; Periodic Boundary Conditions
DispCorr        = no

I tried changing the step size and even the integration method. No luck so far.
I eagerly look forward to any experienced views.

Regards
Hemant

@heman_t this is a new problem, please start a new discussion rather than adding unrelated topics to this one.