[gmx-users] Parametrisation of the cyclic nucleotides in Gromos force fields

James Starlight jmsstarlight at gmail.com
Fri Dec 7 16:41:47 CET 2012


Today I've tried to simulate complexes of my protein with the cyclic
GMP parametrized by ATB's. (below the recent parametrisation for
charges of that molecule done by am1 algorithm)

[ moleculetype ]
; Name   nrexcl
_N4P     3
[ atoms ]
;  nr  type  resnr  resid  atom  cgnr  charge    mass    total_charge
    1    NT    1    _N4P     N2    1   -0.848  14.0067
    2     H    1    _N4P    H22    1    0.424   1.0080
    3     H    1    _N4P    H21    1    0.424   1.0080      ;  0.000
    4    NR    1    _N4P     N1    2   -0.684  14.0067
    5     H    1    _N4P     H1    2    0.437   1.0080
    6     C    1    _N4P     C2    2    0.779  12.0110
    7    NR    1    _N4P     N3    2   -0.678  14.0067
    8     C    1    _N4P     C4    2    0.440  12.0110
    9    NR    1    _N4P     N9    2   -0.294  14.0067      ;  0.000
   10     C    1    _N4P     C8    3    0.272  12.0110
   11    HC    1    _N4P    H01    3    0.141   1.0080
   12     O    1    _N4P     O6    3   -0.555  15.9994
   13     C    1    _N4P     C6    3    0.608  12.0110
   14     C    1    _N4P     C5    3    0.101  12.0110
   15    NR    1    _N4P     N7    3   -0.567  14.0067      ;  0.000
   16    OE    1    _N4P    O4*    4   -0.451  15.9994
   17   CH1    1    _N4P    C1*    4    0.451  13.0190      ;  0.000
   18    OA    1    _N4P    O5*    5   -0.394  15.9994
   19     P    1    _N4P    PAQ    5    0.974  30.9738
   20    OM    1    _N4P    OAR    5   -0.616  15.9994
   21    OA    1    _N4P    O3*    5   -0.390  15.9994
   22    OA    1    _N4P    OAS    5   -0.584  15.9994
   23     H    1    _N4P    H03    5    0.491   1.0080
   24   CH2    1    _N4P    C5*    5    0.281  14.0270
   25   CH1    1    _N4P    C4*    5    0.238  13.0190      ;  0.000
   26   CH1    1    _N4P    C3*    6    0.000  13.0190      ;  0.000
   27   CH1    1    _N4P    C2*    7    0.181  13.0190
   28    OA    1    _N4P    O2*    7   -0.645  15.9994
   29     H    1    _N4P    H8M    7    0.464   1.0080      ;  0.000

In all cases my system have always been crushed after equilibration
run ( during that phase with the posres applied on both protein as
well as ligand the system was stabile) with the errors like

Step 19, time 0.038 (ps)  LINCS WARNING
relative constraint deviation after LINCS:
rms 1.203662, max 11.750027 (between atoms 4289 and 4287)
bonds that rotated more than 30 degrees:
 atom 1 atom 2  angle  previous, current, constraint length
   4288   4287   89.5    0.2277   1.1291      0.1000
   4292   4287   90.5    0.1304   0.9898      0.1350
   4289   4287   90.4    0.1056   1.2750      0.1000
   4318   4303   30.8    0.1531   0.1816      0.1530
   4304   4303   45.2    0.1097   0.1531      0.1090
   4309   4310   90.0    0.2629   0.3419      0.1000
   4299   4290   84.2    0.1404   0.1641      0.1400
   4292   4290   89.4    0.1362   0.5025      0.1380
   4291   4290   89.2    0.1563   0.2142      0.1000
   4293   4292   89.1    0.1252   0.5682      0.1320
   4294   4293   78.1    0.1387   0.3906      0.1350
   4300   4294   92.2    0.1385   0.4639      0.1390
   4295   4294   91.1    0.1365   0.5711      0.1380
   4303   4295   43.4    0.1482   0.1954      0.1470
   4296   4295   36.6    0.1408   0.1593      0.1400
   4301   4296   89.9    0.1323   0.5162      0.1320
   4297   4296   32.5    0.1089   0.1343      0.1090
   4299   4298   87.0    0.1230   0.2758      0.1230
   4300   4299   89.8    0.1431   0.5922      0.1430
   4301   4300   79.0    0.1381   0.1928      0.1380


Fatal error:
1 particles communicated to PME node 26 are more than 2/3 times the
cut-off out of the domain decomposition cell of their charge group in
dimension y.
This usually means that your system is not well equilibrated.
For more information and tips for troubleshooting, please check the GROMACS

After that my system have been crashed and than produced many
step*.pdb files in the work dirr.

It's intresting that with the prodrg topology of that mollecule ( with
worst charge distribution) I've never such problems. Might that error
be due to the wrong geometry parametrisation (e.g incorect dihedrals)
of the cGMP made by ATB ?


James

2012/12/6 James Starlight <jmsstarlight at gmail.com>:
> Justin,
>
> Thanks again for explanation.
>
>
> It's interesting that above parametrization made by ATB have cased the
> system to crash within first ps of modeling ;) (On the contrarythe
> system with the ligand made by prodrg have been very stable during
> 100ns). I ve tried to re-parametrized my molecule by another algorithm
> implemented in ATB ( am1 instead of pm3 which was used in the crashed
> simulation).
>
>
> James
>
> 2012/12/6, Justin Lemkul <jalemkul at vt.edu>:
>>
>>
>> On 12/6/12 2:39 AM, James Starlight wrote:
>>> Justin,
>>>
>>> Could you provide me with the example of the server where I could
>>> obtain Gromac's itp topologies for the charmm ff? I know many such
>>> servers which could be useful only for preparation systems for NAMD
>>> program.
>>>
>>
>> Google "CHARMM ligand topology in Gromacs" (without the quotes) - the first
>>
>> result is what you're looking for.
>>
>>>
>>> By the way recently I've made parametrization of my cGMP molecule by
>>> means of ATB server. In the below example you can see that the charge
>>> distribution is differs from the PRODRG example of that molecule which
>>> I've posted yesterday. Does that charge distribution more suitable for
>>> the 54a force field?
>>>
>>
>> Given that PRODRG generally produces very bad charges, just about anything
>> is
>> better ;)
>>
>> Nucleotide parameters already exist in 54A7, I don't see why you necessarily
>>
>> have to create them from scratch.  In general, these charges look pretty
>> good,
>> but note that DGUA already exists and can describe most of your molecule
>> already.  The cyclic part is the only trick, but the nucleobase parameters
>> should be the same in cGMP and DGUA, given the nature of Gromos96
>> parameterization.
>>
>> -Justin
>>
>>> [ atoms ]
>>> ;  nr  type  resnr  resid  atom  cgnr  charge    mass    total_charge
>>>      1    NT    1    _N4H     N2    1   -0.832  14.0067
>>>      2     H    1    _N4H    H22    1    0.416   1.0080
>>>      3     H    1    _N4H    H21    1    0.416   1.0080      ;  0.000
>>>      4    NR    1    _N4H     N1    2   -0.715  14.0067
>>>      5     H    1    _N4H     H1    2    0.427   1.0080
>>>      6     C    1    _N4H     C2    2    0.775  12.0110
>>>      7    NR    1    _N4H     N3    2   -0.691  14.0067
>>>      8     C    1    _N4H     C4    2    0.431  12.0110
>>>      9    NR    1    _N4H     N9    2   -0.227  14.0067      ;  0.000
>>>     10     C    1    _N4H     C8    3    0.220  12.0110
>>>     11    HC    1    _N4H    H01    3    0.162   1.0080
>>>     12     O    1    _N4H     O6    3   -0.556  15.9994
>>>     13     C    1    _N4H     C6    3    0.669  12.0110
>>>     14     C    1    _N4H     C5    3    0.026  12.0110
>>>     15    NR    1    _N4H     N7    3   -0.521  14.0067      ;  0.000
>>>     16    OE    1    _N4H    O4*    4   -0.429  15.9994
>>>     17   CH1    1    _N4H    C1*    4    0.429  13.0190      ;  0.000
>>>     18   CH1    1    _N4H    C4*    5    0.000  13.0190      ;  0.000
>>>     19    OA    1    _N4H    O5*    6   -0.422  15.9994
>>>     20     P    1    _N4H    PAQ    6    0.971  30.9738
>>>     21    OM    1    _N4H    OAR    6   -0.613  15.9994
>>>     22    OA    1    _N4H    O3*    6   -0.382  15.9994
>>>     23    OA    1    _N4H    OAS    6   -0.617  15.9994
>>>     24     H    1    _N4H    H03    6    0.497   1.0080
>>>     25   CH2    1    _N4H    C5*    6    0.319  14.0270
>>>     26   CH1    1    _N4H    C3*    6    0.247  13.0190      ; -0.000
>>>     27   CH1    1    _N4H    C2*    7    0.200  13.0190
>>>     28    OA    1    _N4H    O2*    7   -0.614  15.9994
>>>     29     H    1    _N4H    H8M    7    0.414   1.0080      ;  0.000
>>>
>>>
>>>
>>> James
>>>
>>> 2012/12/5 Justin Lemkul <jalemkul at vt.edu>:
>>>>
>>>>
>>>> On 12/5/12 1:39 PM, James Starlight wrote:
>>>>>
>>>>> Justin,
>>>>>
>>>>> Indeed the force field is the 54a7 ( modiffied version of the 54a6).
>>>>>
>>>>> The main reason of using GROMOS ff in that case was the topology of
>>>>> ligands which could be easily created by means of prodrg or ATB. On
>>>>> other hand I've never worked with the protein-ligand complexes in
>>>>> charmm ff for instance.
>>>>>
>>>>
>>>> Well, you get out what you put in.  A recent paper
>>>> (dx.doi.org/10.1002/jcc.23055) showed that Gromos force fields performed
>>>> very poorly for simulating nucleic acids.  There are others, but that's
>>>> just
>>>> a recent one.  If you're choosing a force field because it makes life
>>>> easy,
>>>> be prepared to defend your results if they are of poor quality or defend
>>>> a
>>>> lot of wasted time while you re-do the simulations :)
>>>>
>>>> There are servers that produce CHARMM topologies and other programs that
>>>> will convert AMBER topologies into Gromacs format as well.  I would
>>>> suggest
>>>> you evaluate all the options available.
>>>>
>>>>
>>>>> By the way is there any suitable builing blocks (implemented in the
>>>>> rtp enties of the gromos ff) which could be used for charge
>>>>> assignment?
>>>>>
>>>>
>>>> That depends on the functional group.  If it's also found in proteins,
>>>> yes.
>>>> If not, then maybe but probably not.
>>>>
>>>>
>>>> -Justin
>>>> --
>>>> ========================================
>>>>
>>>> Justin A. Lemkul, Ph.D.
>>>> Research Scientist
>>>> Department of Biochemistry
>>>> Virginia Tech
>>>> Blacksburg, VA
>>>> jalemkul[at]vt.edu | (540) 231-9080
>>>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>>>
>>>> ========================================
>>>> --
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>>
>> --
>> ========================================
>>
>> Justin A. Lemkul, Ph.D.
>> Research Scientist
>> Department of Biochemistry
>> Virginia Tech
>> Blacksburg, VA
>> jalemkul[at]vt.edu | (540) 231-9080
>> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
>>
>> ========================================
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