[gmx-users] Why is there a difference between an angle of 0 or 180 deg. for a type 9 proper dihedral with multiplicity of 2?

Christopher Neale chris.neale at alum.utoronto.ca
Sun Jul 5 15:10:20 CEST 2015


Dear Justin:

here is a topology followed by initial coordinates (in which the rings of both Phe are planar, straight out of molefacture/pdb2gmx). Run this in EM or MD and the SC ring of Phe #1 will distort. However, replace "0   15.1669998 2" by "180   15.1669998 2" and everything is groovy.

Chris.

###########################################
### TOPOLOGY
;
;       File 'topol.top' was generated
;       By user: lh824914 (36108)
;       On host: headnode.rit.albany.edu
;       At date: Sat Jul  4 23:10:10 2015
;
;       This is a standalone topology file
;
;       It was generated using program:
;       pdb2gmx - VERSION 4.6.3
;
;       Command line was:
;       pdb2gmx -f FF.gro -ignh
;
;       Force field was read from the standard Gromacs share directory.
;

; Include forcefield parameters
#include "amber99.ff/forcefield.itp"

[ moleculetype ]
; Name            nrexcl
Protein             3

[ atoms ]
;   nr       type  resnr residue  atom   cgnr     charge       mass  typeB    chargeB      massB
; residue   1 PHE rtp NPHE q +1.0
     1         N3      1    PHE      N      1     0.1737      14.01   ; qtot 0.1737
     2          H      1    PHE     H1      2     0.1921      1.008   ; qtot 0.3658
     3          H      1    PHE     H2      3     0.1921      1.008   ; qtot 0.5579
     4          H      1    PHE     H3      4     0.1921      1.008   ; qtot 0.75
     5         CT      1    PHE     CA      5     0.0733      12.01   ; qtot 0.8233
     6         HP      1    PHE     HA      6     0.1041      1.008   ; qtot 0.9274
     7         CT      1    PHE     CB      7      0.033      12.01   ; qtot 0.9604
     8         HC      1    PHE    HB1      8     0.0104      1.008   ; qtot 0.9708
     9         HC      1    PHE    HB2      9     0.0104      1.008   ; qtot 0.9812
    10         CA      1    PHE     CG     10     0.0031      12.01   ; qtot 0.9843
    11         CA      1    PHE    CD1     11    -0.1392      12.01   ; qtot 0.8451
    12         HA      1    PHE    HD1     12     0.1374      1.008   ; qtot 0.9825
    13         CA      1    PHE    CE1     13    -0.1602      12.01   ; qtot 0.8223
    14         HA      1    PHE    HE1     14     0.1433      1.008   ; qtot 0.9656
    15         CA      1    PHE     CZ     15    -0.1208      12.01   ; qtot 0.8448
    16         HA      1    PHE     HZ     16     0.1329      1.008   ; qtot 0.9777
    17         CA      1    PHE    CE2     17    -0.1603      12.01   ; qtot 0.8174
    18         HA      1    PHE    HE2     18     0.1433      1.008   ; qtot 0.9607
    19         CA      1    PHE    CD2     19    -0.1391      12.01   ; qtot 0.8216
    20         HA      1    PHE    HD2     20     0.1374      1.008   ; qtot 0.959
    21          C      1    PHE      C     21     0.6123      12.01   ; qtot 1.571
    22          O      1    PHE      O     22    -0.5713         16   ; qtot 1
; residue   2 PHE rtp CPHE q -1.0
    23          N      2    PHE      N     23    -0.3821      14.01   ; qtot 0.6179
    24          H      2    PHE      H     24     0.2681      1.008   ; qtot 0.886
    25         CT      2    PHE     CA     25    -0.1825      12.01   ; qtot 0.7035
    26         H1      2    PHE     HA     26     0.1098      1.008   ; qtot 0.8133
    27         CT      2    PHE     CB     27    -0.0959      12.01   ; qtot 0.7174
    28         HC      2    PHE    HB1     28     0.0443      1.008   ; qtot 0.7617
    29         HC      2    PHE    HB2     29     0.0443      1.008   ; qtot 0.806
    30         CA      2    PHE     CG     30     0.0552      12.01   ; qtot 0.8612
    31         CA      2    PHE    CD1     31      -0.13      12.01   ; qtot 0.7312
    32         HA      2    PHE    HD1     32     0.1408      1.008   ; qtot 0.872
    33         CA      2    PHE    CE1     33    -0.1847      12.01   ; qtot 0.6873
    34         HA      2    PHE    HE1     34     0.1461      1.008   ; qtot 0.8334
    35         CA      2    PHE     CZ     35    -0.0944      12.01   ; qtot 0.739
    36         HA      2    PHE     HZ     36      0.128      1.008   ; qtot 0.867
    37         CA      2    PHE    CE2     37    -0.1847      12.01   ; qtot 0.6823
    38         HA      2    PHE    HE2     38     0.1461      1.008   ; qtot 0.8284
    39         CA      2    PHE    CD2     39      -0.13      12.01   ; qtot 0.6984
    40         HA      2    PHE    HD2     40     0.1408      1.008   ; qtot 0.8392
    41          C      2    PHE      C     41      0.766      12.01   ; qtot 1.605
    42         O2      2    PHE    OC1     42    -0.8026         16   ; qtot 0.8026
    43         O2      2    PHE    OC2     43    -0.8026         16   ; qtot 0

[ bonds ]
;  ai    aj funct            c0            c1            c2            c3
    1     2     1
    1     3     1
    1     4     1
    1     5     1
    5     6     1
    5     7     1
    5    21     1
    7     8     1
    7     9     1
    7    10     1
   10    11     1
   10    19     1
   11    12     1
   11    13     1
   13    14     1
   13    15     1
   15    16     1
   15    17     1
   17    18     1
   17    19     1
   19    20     1
   21    22     1
   21    23     1
   23    24     1
   23    25     1
   25    26     1
   25    27     1
   25    41     1
   27    28     1
   27    29     1
   27    30     1
   30    31     1
   30    39     1
   31    32     1
   31    33     1
   33    34     1
   33    35     1
   35    36     1
   35    37     1
   37    38     1
   37    39     1
   39    40     1
   41    42     1
   41    43     1

[ pairs ]
;  ai    aj funct            c0            c1            c2            c3
    1     8     1
    1     9     1
    1    10     1
    1    22     1
    1    23     1
    2     6     1
    2     7     1
    2    21     1
    3     6     1
    3     7     1
    3    21     1
    4     6     1
    4     7     1
    4    21     1
    5    11     1
    5    19     1
    5    24     1
    5    25     1
    6     8     1
    6     9     1
    6    10     1
    6    22     1
    6    23     1
    7    12     1
    7    13     1
    7    17     1
    7    20     1
    7    22     1
    7    23     1
    8    11     1
    8    19     1
    8    21     1
    9    11     1
    9    19     1
    9    21     1
   10    14     1
   10    15     1
   10    18     1
   10    21     1
   11    16     1
   11    17     1
   11    20     1
   12    14     1
   12    15     1
   12    19     1
   13    18     1
   13    19     1
   14    16     1
   14    17     1
   15    20     1
   16    18     1
   16    19     1
   18    20     1
   21    26     1
   21    27     1
   21    41     1
   22    24     1
   22    25     1
   23    28     1
   23    29     1
   23    30     1
   23    42     1
   23    43     1
   24    26     1
   24    27     1
   24    41     1
   25    31     1
   25    39     1
   26    28     1
   26    29     1
   26    30     1
   26    42     1
   26    43     1
   27    32     1
   27    33     1
   27    37     1
   27    40     1
   27    42     1
   27    43     1
   28    31     1
   28    39     1
   28    41     1
   29    31     1
   29    39     1
   29    41     1
   30    34     1
   30    35     1
   30    38     1
   30    41     1
   31    36     1
   31    37     1
   31    40     1
   32    34     1
   32    35     1
   32    39     1
   33    38     1
   33    39     1
   34    36     1
   34    37     1
   35    40     1
   36    38     1
   36    39     1
   38    40     1

[ angles ]
;  ai    aj    ak funct            c0            c1            c2            c3
    2     1     3     1
    2     1     4     1
    2     1     5     1
    3     1     4     1
    3     1     5     1
    4     1     5     1
    1     5     6     1
    1     5     7     1
    1     5    21     1
    6     5     7     1
    6     5    21     1
    7     5    21     1
    5     7     8     1
    5     7     9     1
    5     7    10     1
    8     7     9     1
    8     7    10     1
    9     7    10     1
    7    10    11     1
    7    10    19     1
   11    10    19     1
   10    11    12     1
   10    11    13     1
   12    11    13     1
   11    13    14     1
   11    13    15     1
   14    13    15     1
   13    15    16     1
   13    15    17     1
   16    15    17     1
   15    17    18     1
   15    17    19     1
   18    17    19     1
   10    19    17     1
   10    19    20     1
   17    19    20     1
    5    21    22     1
    5    21    23     1
   22    21    23     1
   21    23    24     1
   21    23    25     1
   24    23    25     1
   23    25    26     1
   23    25    27     1
   23    25    41     1
   26    25    27     1
   26    25    41     1
   27    25    41     1
   25    27    28     1
   25    27    29     1
   25    27    30     1
   28    27    29     1
   28    27    30     1
   29    27    30     1
   27    30    31     1
   27    30    39     1
   31    30    39     1
   30    31    32     1
   30    31    33     1
   32    31    33     1
   31    33    34     1
   31    33    35     1
   34    33    35     1
   33    35    36     1
   33    35    37     1
   36    35    37     1
   35    37    38     1
   35    37    39     1
   38    37    39     1
   30    39    37     1
   30    39    40     1
   37    39    40     1
   25    41    42     1
   25    41    43     1
   42    41    43     1

[ dihedrals ]
;  ai    aj    ak    al funct            c0            c1            c2            c3            c4            c5
    2     1     5     6     9
    2     1     5     7     9
    2     1     5    21     9
    3     1     5     6     9
    3     1     5     7     9
    3     1     5    21     9
    4     1     5     6     9
    4     1     5     7     9
    4     1     5    21     9
    1     5     7     8     9
    1     5     7     9     9
    1     5     7    10     9
    6     5     7     8     9
    6     5     7     9     9
    6     5     7    10     9
   21     5     7     8     9
   21     5     7     9     9
   21     5     7    10     9
    1     5    21    22     9
    1     5    21    23     9
    6     5    21    22     9
    6     5    21    23     9
    7     5    21    22     9
    7     5    21    23     9
    5     7    10    11     9
    5     7    10    19     9
    8     7    10    11     9
    8     7    10    19     9
    9     7    10    11     9
    9     7    10    19     9
    7    10    11    12     9   0   15.1669998 2
    7    10    11    13     9   0   15.1669998 2
   19    10    11    12     9   0   15.1669998 2
   19    10    11    13     9   0   15.1669998 2
    7    10    19    17     9   0   15.1669998 2
    7    10    19    20     9   0   15.1669998 2
   11    10    19    17     9   0   15.1669998 2
   11    10    19    20     9   0   15.1669998 2
   10    11    13    14     9   0   15.1669998 2
   10    11    13    15     9   0   15.1669998 2
   12    11    13    14     9   0   15.1669998 2
   12    11    13    15     9   0   15.1669998 2
   11    13    15    16     9   0   15.1669998 2
   11    13    15    17     9   0   15.1669998 2
   14    13    15    16     9   0   15.1669998 2
   14    13    15    17     9   0   15.1669998 2
   13    15    17    18     9   0   15.1669998 2
   13    15    17    19     9   0   15.1669998 2
   16    15    17    18     9   0   15.1669998 2
   16    15    17    19     9   0   15.1669998 2
   15    17    19    10     9   0   15.1669998 2
   15    17    19    20     9   0   15.1669998 2
   18    17    19    10     9   0   15.1669998 2
   18    17    19    20     9   0   15.1669998 2
    5    21    23    24     9
    5    21    23    25     9
   22    21    23    24     9
   22    21    23    25     9
   21    23    25    26     9
   21    23    25    27     9
   21    23    25    41     9
   24    23    25    26     9
   24    23    25    27     9
   24    23    25    41     9
   23    25    27    28     9
   23    25    27    29     9
   23    25    27    30     9
   26    25    27    28     9
   26    25    27    29     9
   26    25    27    30     9
   41    25    27    28     9
   41    25    27    29     9
   41    25    27    30     9
   23    25    41    42     9
   23    25    41    43     9
   26    25    41    42     9
   26    25    41    43     9
   27    25    41    42     9
   27    25    41    43     9
   25    27    30    31     9
   25    27    30    39     9
   28    27    30    31     9
   28    27    30    39     9
   29    27    30    31     9
   29    27    30    39     9
   27    30    31    32     9
   27    30    31    33     9
   39    30    31    32     9
   39    30    31    33     9
   27    30    39    37     9
   27    30    39    40     9
   31    30    39    37     9
   31    30    39    40     9
   30    31    33    34     9
   30    31    33    35     9
   32    31    33    34     9
   32    31    33    35     9
   31    33    35    36     9
   31    33    35    37     9
   34    33    35    36     9
   34    33    35    37     9
   33    35    37    38     9
   33    35    37    39     9
   36    35    37    38     9
   36    35    37    39     9
   35    37    39    30     9
   35    37    39    40     9
   38    37    39    30     9
   38    37    39    40     9

[ dihedrals ]
;  ai    aj    ak    al funct            c0            c1            c2            c3
    5    23    21    22     4
    7    10    19    11     4
   10    13    11    12     4
   10    17    19    20     4
   11    15    13    14     4
   13    17    15    16     4
   15    19    17    18     4
   21    25    23    24     4
   25    42    41    43     4
   27    30    39    31     4
   30    33    31    32     4
   30    37    39    40     4
   31    35    33    34     4
   33    37    35    36     4
   35    39    37    38     4

; Include Position restraint file
#ifdef POSRES
#include "posre.itp"
#endif

; Include water topology
#include "amber99.ff/tip3p.itp"

#ifdef POSRES_WATER
; Position restraint for each water oxygen
[ position_restraints ]
;  i funct       fcx        fcy        fcz
   1    1       1000       1000       1000
#endif

; Include topology for ions
#include "amber99.ff/ions.itp"

[ system ]
; Name
Gallium Rubidium Oxygen Manganese Argon Carbon Silicon

[ molecules ]
; Compound        #mols
Protein             1



###########################################
### INITIAL COORDINATES

Gallium Rubidium Oxygen Manganese Argon Carbon Silicon
   43
    1PHE      N    1  -0.013   0.245  -0.011
    1PHE     H1    2  -0.082   0.296   0.040
    1PHE     H2    3   0.064   0.225   0.049
    1PHE     H3    4   0.018   0.300  -0.088
    1PHE     CA    5  -0.070   0.121  -0.060
    1PHE     HA    6  -0.146   0.146  -0.120
    1PHE     CB    7   0.036   0.047  -0.136
    1PHE    HB1    8   0.122   0.085  -0.102
    1PHE    HB2    9   0.023   0.076  -0.231
    1PHE     CG   10   0.058  -0.104  -0.142
    1PHE    CD1   11  -0.017  -0.189  -0.060
    1PHE    HD1   12  -0.085  -0.151   0.003
    1PHE    CE1   13   0.003  -0.327  -0.067
    1PHE    HE1   14  -0.051  -0.388  -0.009
    1PHE     CZ   15   0.098  -0.380  -0.155
    1PHE     HZ   16   0.112  -0.479  -0.160
    1PHE    CE2   17   0.173  -0.294  -0.237
    1PHE    HE2   18   0.241  -0.331  -0.300
    1PHE    CD2   19   0.152  -0.155  -0.230
    1PHE    HD2   20   0.205  -0.093  -0.288
    1PHE      C   21  -0.122   0.034   0.054
    1PHE      O   22  -0.052  -0.053   0.105
    2PHE      N   23  -0.243   0.056   0.096
    2PHE      H   24  -0.298   0.127   0.053
    2PHE     CA   25  -0.300  -0.022   0.206
    2PHE     HA   26  -0.301  -0.118   0.177
    2PHE     CB   27  -0.214  -0.007   0.327
    2PHE    HB1   28  -0.258   0.067   0.379
    2PHE    HB2   29  -0.127   0.025   0.291
    2PHE     CG   30  -0.179  -0.115   0.430
    2PHE    CD1   31  -0.241  -0.240   0.424
    2PHE    HD1   32  -0.309  -0.259   0.353
    2PHE    CE1   33  -0.208  -0.338   0.518
    2PHE    HE1   34  -0.252  -0.428   0.514
    2PHE     CZ   35  -0.113  -0.311   0.618
    2PHE     HZ   36  -0.090  -0.381   0.685
    2PHE    CE2   37  -0.051  -0.185   0.623
    2PHE    HE2   38   0.016  -0.165   0.694
    2PHE    CD2   39  -0.084  -0.087   0.528
    2PHE    HD2   40  -0.040   0.003   0.531
    2PHE      C   41  -0.442   0.022   0.236
    2PHE    OC1   42  -0.493  -0.024   0.309
    2PHE    OC2   43  -0.496   0.113   0.173
  10.00000  10.00000  10.00000



________________________________________
From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Justin Lemkul <jalemkul at vt.edu>
Sent: 05 July 2015 08:52
To: gmx-users at gromacs.org
Subject: Re: [gmx-users] Why is there a difference between an angle of 0 or 180 deg. for a type 9 proper dihedral with multiplicity of 2?

On 7/5/15 12:56 AM, Christopher Neale wrote:
> Dear Justin:
>
> Thank you for your help. I am glad to see that I was not way out to lunch in my interpretation of multiplicity and proper dihedral angles.
>
> First, the out-of-plane motions are not minor. Even just in EM, the dihedral angles along the main ring convert from near 0 deg to about 50 deg, so I think that we're into the neighbourhood of major problems here. Second, my test system was a single ring, like benzene but with a couple of substituents. However, I can reproduce this issue in a standard molecule as follows, so I do not think that the issue has anything to do with my exotic molecule. Take any peptide/protein with a phenylalanine. There are 24 proper dihedral angles around the PHE sidechain ring in the amber99 force field. In this force field, these dihedral angles are all 180 deg / Fc=15.1669998 / mult=2. I take my toplogy out of pdb2gmx and specify these parameters in the .top file and run EM and I still get the planar ring, as expected. Now I simply change those N=24 occurrences of 180 deg to 0 deg (still multiplicity=2) and I run EM and I get these ~50 deg dihedral angles around the ring. This is still wit!
 h g
>   romacs 4.6.3. I have not checked with other versions of gromacs.
>
> If you make a PHE-PHE peptide in VMD with molefacture (2 aa's to avoid the problem amber has with a single amino acid and the termini), then run it through pdb2gmx (v. 4.6.3) the lines in the [ dihedrals ] section that need modification to adjust the proper dihedral angles in the ring of the first PHE sidechain are:
>
>      7    10    11    12     9   0   15.1669998 2
>      7    10    11    13     9   0   15.1669998 2
>     19    10    11    12     9   0   15.1669998 2
>     19    10    11    13     9   0   15.1669998 2
>      7    10    19    17     9   0   15.1669998 2
>      7    10    19    20     9   0   15.1669998 2
>     11    10    19    17     9   0   15.1669998 2
>     11    10    19    20     9   0   15.1669998 2
>     10    11    13    14     9   0   15.1669998 2
>     10    11    13    15     9   0   15.1669998 2
>     12    11    13    14     9   0   15.1669998 2
>     12    11    13    15     9   0   15.1669998 2
>     11    13    15    16     9   0   15.1669998 2
>     11    13    15    17     9   0   15.1669998 2
>     14    13    15    16     9   0   15.1669998 2
>     14    13    15    17     9   0   15.1669998 2
>     13    15    17    18     9   0   15.1669998 2
>     13    15    17    19     9   0   15.1669998 2
>     16    15    17    18     9   0   15.1669998 2
>     16    15    17    19     9   0   15.1669998 2
>     15    17    19    10     9   0   15.1669998 2
>     15    17    19    20     9   0   15.1669998 2
>     18    17    19    10     9   0   15.1669998 2
>     18    17    19    20     9   0   15.1669998 2
>

Can you send the full topology, or at least the [atoms] section?  I can't
decipher what these actually should be.

-Justin

> where I get the bizarre conformations when I use the above, but if I switch the "0"'s to "180"'s (recovering the original force field) then I get a planar ring.
>
> Therefore, I think that either I am misunderstanding something about proper dihedrals and multiplicity = 2 or there is a more serious problem. What I don't understand at this point is that the force fields (amber at least) actually contain quite a few proper dihedrals that do use angle = 0 and multiplicity = 2, so what is special aboutthe PHE test case outlined above that leads them to not work whereas they are obviously intended to work.
>
> I'll take a look into other gromacs versions when I have a chance and will report back.
>
> Thank you,
> Chris.
>
> ________________________________________
> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Justin Lemkul <jalemkul at vt.edu>
> Sent: 04 July 2015 09:41
> To: gmx-users at gromacs.org
> Subject: Re: [gmx-users] Why is there a difference between an angle of 0 or 180 deg. for a type 9 proper dihedral with multiplicity of 2?
>
> On 7/4/15 3:32 AM, Christopher Neale wrote:
>> Dear Gromacs users:
>>
>> I have been working on creating a topology for an exotic molecule. It
>> contains aromatic rings and my parameters always seemed to allow the rings to
>> buckle and become non-planer, much like a glucose ring would (though a little
>> less extensively). However, I have managed to solve the problem by switching
>> my proper (type 9) dihedral angles from angle = 0 degrees, multiplicity = 2
>> to angle = 180 degrees, multiplicity = 2. I thought that those two conditions
>> should be equivalent and it was only by seriously simplifying the molecule
>> down to a single ring and then toying with every conceivable parameter that I
>> even hit on this. I am using gromacs 4.6.3 and have not tried other versions
>> of gromacs, but this makes so little sense to me that I thought I would ask
>> about it here. There are lots of proper dihedrals in the available force
>> fields that use dihedrals with a set angle of zero degrees, though I do note
>> that for any aromatic ring that I have seen they are always 180 deg (with
>> mul tiplicity of 2 so that they can handle both cis and trans). Presumably I
>> have just missed some obvious definition, but at least I can verify that if I
>> switch even one proper dihedral from angle = 180 back to angle = 0 (with
>> multiplicity = 2 in each case), then I start to see deformation of the ring's
>> planarity.
>>
>
> Some deformation is not necessarily unphysical.  Aromatic rings in CHARMM are
> treated like this, for instance.  It shouldn't be substantial, but it shouldn't
> remain exactly planar, either.  What are the parameters you're using?  The
> choice of 0 vs. 180 here for multiplicity = 2 should indeed be irrelevant.  Have
> you gone down to something as simple as, e.g. benzene?
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 629
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
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--
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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