[gmx-users] coenzyme-protein complex

Justin Lemkul jalemkul at vt.edu
Wed Jan 8 03:21:53 CET 2014



On 1/7/14, 1:45 PM, Mostafa Javaheri wrote:
> Dear J. Lemkul
>  >> 3. I merged these two ligands into one mol2 file and
>  >> sent it to the swissparam, then followed the rest of steps, is this OK or
>  >> should I send them separately?
>
>  >They should probably be treated individually.
>
> I treated these two ligands individually and faced the following error when run
> this command
>
> grompp -f em.mdp -c solvated.pdb -p topol.top
>
> ***********************
> Program grompp, VERSION 4.6.4
> Source code file: /home/MJ-centos/programfiles/gromacs-4.6.4/src/kernel/topio.c,
> line: 734
>
> Fatal error:
> Syntax error - File GTP.itp, line 7
> Last line read:
> '[ atomtypes ] '
> Invalid order for directive atomtypes
> For more information and tips for troubleshooting, please check the GROMACS
> website at http://www.gromacs.org/Documentation/Errors
> ************************
>

The [atomtypes] directive is at the force field level, so any new [atomtypes] 
need to be declared before any [moleculetypes] appear in the topology.  See 
Chapter 5 for the required hierarchy.

> I added ligands to the end of conf.pdb file and modified topol.top too (these
> files uploaded for more details), but when I treat each of them separately no
> error will appear and I'll face just the following notes, am I doing something
> wrong?
>
> *************************
>    Ignoring obsolete mdp entry 'title'
>
> NOTE 1 [file em.mdp]:
>    The switch/shift interaction settings are just for compatibility; you
>    will get better performance from applying potential modifiers to your
>    interactions!
>
>
>
> NOTE 2 [file em.mdp]:
>    For energy conservation with switch/shift potentials, rlist should be 0.1
>    to 0.3 nm larger than rvdw.
>

These notes indicate possible problems with the .mdp file, but since you haven't 
provided that file, it's impossible to say what may or may not be wrong.  Notes 
don't necessarily indicate real problems, but they often catch things that could 
be bad.

-Justin

> Generated 24310 of the 24310 non-bonded parameter combinations
> Generating 1-4 interactions: fudge = 1
> Generated 21172 of the 24310 1-4 parameter combinations
> Excluding 3 bonded neighbours molecule type 'Protein_chain_A'
> Excluding 3 bonded neighbours molecule type 'Other_chain_A2'
> Excluding 3 bonded neighbours molecule type 'GDP'
> Excluding 2 bonded neighbours molecule type 'SOL'
>
> NOTE 3 [file topol.top, line 48]:
>    System has non-zero total charge: -43.999989
>    Total charge should normally be an integer. See
>    http://www.gromacs.org/Documentation/Floating_Point_Arithmetic
>    for discussion on how close it should be to an integer.
>
>
>
> Analysing residue names:
> There are:   899    Protein residues
> There are:     3      Other residues
> There are: 48875      Water residues
> Analysing Protein...
> Analysing residues not classified as Protein/DNA/RNA/Water and splitting into
> groups...
> Number of degrees of freedom in T-Coupling group rest is 334845.00
> Largest charge group radii for Van der Waals: 0.039, 0.039 nm
> Largest charge group radii for Coulomb:       0.084, 0.084 nm
>
> NOTE 4 [file em.mdp]:
>    The sum of the two largest charge group radii (0.078024) is larger than
>    rlist (1.200000) - rvdw (1.200000).
>    With exact cut-offs, better performance can be obtained with
>    cutoff-scheme = Verlet, because it does not use charge groups at all.
>
> Calculating fourier grid dimensions for X Y Z
> Using a fourier grid of 108x108x108, spacing 0.118 0.118 0.118
> Estimate for the relative computational load of the PME mesh part: 0.17
> This run will generate roughly 12 Mb of data
>
> There were 4 notes
> ****************************
>
> *************************
> ; Include forcefield parameters
> #include "charmm27.ff/forcefield.itp"
>
> ; Include chain topologies
> #include "GDP.itp"
> #include "GTP.itp"
> #include "topol_Protein_chain_A.itp"
> #include "topol_Other_chain_A2.itp"
>
> ; Include water topology
> #include "charmm27.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 "charmm27.ff/ions.itp"
>
> [ system ]
> ; Name
> A1CBIII in water
>
> [ molecules ]
> ; Compound        #mols
> Protein_chain_A     1
> Other_chain_A2      2
> GDP                 1
> GTP                 1
> **************************
> topol.top
>
> **************************
> ATOM  13821  HZ3 LYS A 450      30.059   9.034  11.305  1.00  0.00
> ATOM  13822 C    LYS A 450      25.373   4.382  14.445  1.00  0.00           C
> ATOM  13823  OT1 LYS A 450      24.583   4.846  13.578  1.00  0.00           O
> ATOM  13824  OT2 LYS A 450      25.029   4.012  15.600  1.00  0.00           O
> ATOM  13825  MG   MG A 502      18.842  20.898 -18.829  1.00  0.00
> ATOM  13826  MG   MG A 503      22.122 -11.947 -46.475  1.00  0.00
> ATOM      1  N1  LIG     1      15.320  -7.826 -42.055  1.00  0.00      LIG
> ATOM      2  C2  LIG     1      15.559  -8.569 -40.969  1.00  0.00      LIG
> ATOM      3  N3  LIG     1      16.562  -9.453 -40.896  1.00  0.00      LIG
> ATOM      4  C4  LIG     1      17.388  -9.635 -41.933  1.00  0.00      LIG
> ATOM      5  C5  LIG     1      17.190  -8.858 -43.145  1.00  0.00      LIG
> ATOM      6  C6  LIG     1      16.071  -7.910 -43.148  1.00  0.00      LIG
> ATOM      7  N7  LIG     1      18.142  -9.240 -43.995  1.00  0.00      LIG
> ATOM      8  C8  LIG     1      18.889 -10.176 -43.380  1.00  0.00      LIG
> ATOM      9  N9  LIG     1      18.422 -10.414 -42.154  1.00  0.00      LIG
> ATOM     10  PA  LIG     1      23.028 -10.344 -43.330  1.00  0.00      LIG
> ATOM     11  PB  LIG     1      25.620  -9.375 -44.053  1.00  0.00      LIG
> ATOM     12  HN1 LIG     1      14.522  -7.160 -42.047  1.00  0.00      LIG
> ATOM     13 HN21 LIG     1      13.999  -7.791 -39.898  1.00  0.00      LIG
> ATOM     14 HN22 LIG     1      14.946  -9.000 -39.071  1.00  0.00      LIG
> ATOM     15 HO2' LIG     1      17.694 -14.312 -41.107  1.00  0.00      LIG
> ATOM     16 HO3' LIG     1      19.145 -14.258 -39.324  1.00  0.00      LIG
> ATOM     17  H1' LIG     1      18.474 -11.141 -40.186  1.00  0.00      LIG
> ATOM     18  C1' LIG     1      18.971 -11.324 -41.145  1.00  0.00      LIG
> ATOM     19  O1A LIG     1      22.215 -10.966 -44.397  1.00  0.00      LIG
> ATOM     20  O1B LIG     1      25.597  -8.334 -42.987  1.00  0.00      LIG
> ATOM     21  N2  LIG     1      14.767  -8.443 -39.892  1.00  0.00      LIG
> ATOM     22  H2' LIG     1      18.953 -12.957 -42.525  1.00  0.00      LIG
> ATOM     23  O2' LIG     1      17.693 -13.365 -40.927  1.00  0.00      LIG
> ATOM     24  C2' LIG     1      18.876 -12.794 -41.444  1.00  0.00      LIG
> ATOM     25  O2A LIG     1      22.715  -8.939 -42.977  1.00  0.00      LIG
> ATOM     26  O2B LIG     1      25.137  -8.949 -45.378  1.00  0.00      LIG
> ATOM     27  H3' LIG     1      20.489 -14.209 -41.283  1.00  0.00      LIG
> ATOM     28  O3' LIG     1      19.851 -13.606 -39.393  1.00  0.00      LIG
> ATOM     29  C3' LIG     1      20.108 -13.325 -40.758  1.00  0.00      LIG
> ATOM     30  O3A LIG     1      24.600 -10.498 -43.567  1.00  0.00      LIG
> ATOM     31  O3B LIG     1      26.905 -10.109 -44.110  1.00  0.00      LIG
> ATOM     32  C4' LIG     1      21.106 -12.199 -40.850  1.00  0.00      LIG
> ATOM     33  H4' LIG     1      21.694 -12.150 -39.926  1.00  0.00      LIG
> ATOM     34  O4' LIG     1      20.352 -11.019 -41.028  1.00  0.00      LIG
> ATOM     35  O5' LIG     1      22.921 -11.276 -42.060  1.00  0.00      LIG
> ATOM     36  C5' LIG     1      22.032 -12.368 -42.035  1.00  0.00      LIG
> ATOM     37  O6  LIG     1      15.833  -7.213 -44.138  1.00  0.00      LIG
> ATOM     38  H8  LIG     1      19.743 -10.671 -43.820  1.00  0.00      LIG
> ATOM     39  HC1 LIG     1      21.451 -12.391 -42.957  1.00  0.00      LIG
> ATOM     40  HC2 LIG     1      22.594 -13.296 -41.932  1.00  0.00      LIG
> ATOM      1  N1  LIG     1       9.682  24.014 -12.907  1.00  0.00      LIG
> ATOM      2  C2  LIG     1       9.758  23.159 -11.827  1.00  0.00      LIG
> ATOM      3  N3  LIG     1      10.590  22.064 -11.861  1.00  0.00      LIG
> ATOM      4  C4  LIG     1      11.311  21.834 -13.005  1.00  0.00      LIG
> ATOM      5  C5  LIG     1      11.227  22.665 -14.115  1.00  0.00      LIG
> ATOM      6  C6  LIG     1      10.400  23.782 -14.066  1.00  0.00      LIG
> ATOM      7  N7  LIG     1      12.055  22.162 -15.063  1.00  0.00      LIG
> ATOM      8  C8  LIG     1      12.646  21.043 -14.578  1.00  0.00      LIG
> ATOM      9  N9  LIG     1      12.164  20.814 -13.313  1.00  0.00      LIG
> ATOM     10  PA  LIG     1      16.489  20.307 -14.720  1.00  0.00      LIG
> ATOM     11  PB  LIG     1      19.173  20.886 -15.662  1.00  0.00      LIG
> ATOM     12  PG  LIG     1      20.804  18.982 -17.141  1.00  0.00      LIG
> ATOM     13  HN1 LIG     1       9.071  24.853 -12.849  1.00  0.00      LIG
> ATOM     14 HN21 LIG     1       9.133  22.823  -9.905  1.00  0.00      LIG
> ATOM     15 HN22 LIG     1       8.433  24.232 -10.690  1.00  0.00      LIG
> ATOM     16 HO2' LIG     1      10.561  18.744 -11.934  1.00  0.00      LIG
> ATOM     17 HO3' LIG     1      12.256  17.706 -10.567  1.00  0.00      LIG
> ATOM     18  H1' LIG     1      12.161  19.933 -11.405  1.00  0.00      LIG
> ATOM     19  C1' LIG     1      12.580  19.766 -12.397  1.00  0.00      LIG
> ATOM     20  O1A LIG     1      15.523  20.116 -15.857  1.00  0.00      LIG
> ATOM     21  O1B LIG     1      18.861  21.695 -16.855  1.00  0.00      LIG
> ATOM     22  O1G LIG     1      19.697  19.159 -18.131  1.00  0.00      LIG
> ATOM     23  N2  LIG     1       9.052  23.428 -10.716  1.00  0.00      LIG
> ATOM     24  O2' LIG     1      10.956  18.001 -12.436  1.00  0.00      LIG
> ATOM     25  H2' LIG     1      12.337  18.289 -13.945  1.00  0.00      LIG
> ATOM     26  C2' LIG     1      12.244  18.357 -12.861  1.00  0.00      LIG
> ATOM     27  O2A LIG     1      16.484  21.702 -14.124  1.00  0.00      LIG
> ATOM     28  O2B LIG     1      19.525  21.804 -14.510  1.00  0.00      LIG
> ATOM     29  O2G LIG     1      22.061  19.629 -17.641  1.00  0.00      LIG
> ATOM     30  C3' LIG     1      13.345  17.554 -12.193  1.00  0.00      LIG
> ATOM     31  O3' LIG     1      13.110  17.303 -10.830  1.00  0.00      LIG
> ATOM     32  H3' LIG     1      13.537  16.635 -12.746  1.00  0.00      LIG
> ATOM     33  O3A LIG     1      17.934  19.926 -15.322  1.00  0.00      LIG
> ATOM     34  O3B LIG     1      20.367  19.829 -15.797  1.00  0.00      LIG
> ATOM     35  O3G LIG     1      21.062  17.602 -16.613  1.00  0.00      LIG
> ATOM     36  C4' LIG     1      14.535  18.498 -12.308  1.00  0.00      LIG
> ATOM     37  H4' LIG     1      15.199  18.371 -11.453  1.00  0.00      LIG
> ATOM     38  O4' LIG     1      14.003  19.820 -12.356  1.00  0.00      LIG
> ATOM     39  O5' LIG     1      16.345  19.168 -13.634  1.00  0.00      LIG
> ATOM     40  C5' LIG     1      15.290  18.246 -13.603  1.00  0.00      LIG
> ATOM     41  O6  LIG     1      10.297  24.576 -15.019  1.00  0.00      LIG
> ATOM     42  H8  LIG     1      13.378  20.430 -15.103  1.00  0.00      LIG
> ATOM     43  HC1 LIG     1      15.679  17.228 -13.620  1.00  0.00      LIG
> ATOM     44  HC2 LIG     1      14.630  18.407 -14.456  1.00  0.00      LIG
> TER
> ENDMDL
> ***************************
> conf.pdb
>
>
> On Mon, 01/06/2014 05:30 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>     On 1/6/14, 5:35 AM, Mostafa Javaheri wrote:
>      > ​Dear Gromacs users
>      > I would be grateful if any one answers my questions
>      > 1.
>      > I have two coenzyme (GTP & GDP) and two Ion (Mg) attached to the
>      > hetrodimer protein, I am going to use charmm27 force field for Gromacs
>     simulation and swissparam for achieving the ligands topologies; Could I
>     trust at these topology (.itp) or they need
>      > some charge correction like PRODRG outputs?
>
>     That depends on the quality of the output charges. SwissParam, to my knowledge,
>     does not score the quality of the topology itself, though validation was done
>     based on reproducing binding energies in the original paper. That does not (in
>     my opinion) necessarily guarantee that any topology it produces will be of high
>     quality.
>
>     The ParamChem server provides a more quantitative score of the quality of the
>     topology. The larger the penalty score, the more refinement you need to do.
>     The procedure for improving the topology is published and is also written as a
>     web tutorial. The other benefit of ParamChem is that it has recently been
>     updated to the latest version of the CGenFF parameter set (2b8) and is thus
>     up-to-date with the latest CHARMM force fields (with CHARMM36 representing
>     improvements over CHARMM27).
>
>      > 2. Does anyone have ".mdp" fiels that consist with my system?
>
>     CHARMM parameters have been discussed extensively across the list. The settings
>     are dependent upon the force field, not the contents of the coordinate file.
>
>      > 3. I merged these two ligands into one mol2 file and
>      > sent it to the swissparam, then followed the rest of steps, is this OK or
>      > should I send them separately?
>
>     They should probably be treated individually.
>
>     -Justin
>
>     --
>     ==================================================
>
>     Justin A. Lemkul, Ph.D.
>     Postdoctoral Fellow
>
>     Department of Pharmaceutical Sciences
>     School of Pharmacy
>     Health Sciences Facility II, Room 601
>     University of Maryland, Baltimore
>     20 Penn St.
>     Baltimore, MD 21201
>
>     jalemkul at outerbanks.umaryland.edu <mailto:jalemkul at outerbanks.umaryland.edu>
>     | (410) 706-7441
>
>     ==================================================
>     --
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>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441

==================================================


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