[gmx-users] Re: still can not run md for creatine

Justin A. Lemkul jalemkul at vt.edu
Tue Nov 16 13:02:33 CET 2010



Esteban Gabriel Vega Hissi wrote:
> Justin,
> 
> Regarding the charges you mention, what do you think about RESP charges 
> for this kind of compounds (drugs) parameterization?
> 

We have not found any single charge calculation method that correctly reproduces 
the charges on Gromos96 charge groups, so further iterative refinement and 
validation is a must.  We recommend AM1-BCC for an initial charge calculation, 
as it actually produces charges that are consistently more comparable to those 
expected in the force field.

The groups in Gromos96 are very transferable across molecules, so piecing 
together a novel molecule from building blocks works quite well.  It's only for 
those unknown groups that you'd have to derive new charges.

As soon as our paper is out, I will link it from the Parameterization and PRODRG 
pages on the wiki, since this is a very common question.

-Justin

> Best wishes
> 
> Esteban
> 
> --
> On Mon, Nov 15, 2010 at 11:12 PM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto:jalemkul at vt.edu>> wrote:
> 
> 
>     Just the $0.02 that I always seem to contribute in these types of
>     discussions - the topology you have shown below contains some likely
>     problems.  The charges (and massive charge group size) can lead to
>     artifacts.  We've got a paper due out soon about the implications of
>     incorrect charges, but I would advise you that this topology should
>     *not* be used for production simulation.  You'd be better off
>     spending the time to properly parameterize the molecule rather than
>     run a bunch of simulations and get questionable (at best) or wrong
>     (at worst) results.
> 
>     http://www.gromacs.org/Documentation/How-tos/Parameterization
> 
>     -Justin
> 
>     Olga Ivchenko wrote:
> 
> 
>         Hey Vitaly,
> 
>         Thank you for your reply. Here is the files:
> 
>         *itp:*
>         ;      ;      ;       This file was generated by PRODRG version
>         AA081006.0504
>         ;       PRODRG written/copyrighted by Daan van Aalten
>         ;       and Alexander Schuettelkopf
>         ;      ;       Questions/comments to
>         dava at davapc1.bioch.dundee.ac.uk
>         <mailto:dava at davapc1.bioch.dundee.ac.uk>
>         <mailto:dava at davapc1.bioch.dundee.ac.uk
>         <mailto:dava at davapc1.bioch.dundee.ac.uk>>
> 
>         ;      ;       When using this software in a publication, cite:
>         ;       A. W. Schuettelkopf and D. M. F. van Aalten (2004).
>         ;       PRODRG - a tool for high-throughput crystallography
>         ;       of protein-ligand complexes.
>         ;       Acta Crystallogr. D60, 1355--1363.
>         ;      ;      
>         [ moleculetype ]
>          Name nrexcl
>         DRG      3
> 
>         [ atoms ]
>         ;   nr      type  resnr resid  atom  cgnr   charge     mass
>             1        OM     1  DRG     OXT     1   -0.701  15.9994      
>         2         C     1  DRG       C     1    0.402  12.0110       3  
>              OM     1  DRG       O     1   -0.701  15.9994       4      
>         CH2     1  DRG      CA     2    0.185  14.0270       5         N
>             1  DRG       N     2    0.468  14.0067       6       CH3    
>         1  DRG     CAG     2    0.201  15.0350       7         C     1
>          DRG     CAH     2    0.377  12.0110       8        NZ     1
>          DRG     NAE     2   -0.163  14.0067       9         H     1
>          DRG     HA6     2    0.023   1.0080      10         H     1
>          DRG     HAE     2    0.024   1.0080      11        NZ     1
>          DRG     NAD     2   -0.163  14.0067      12         H     1
>          DRG     HA5     2    0.024   1.0080      13         H     1
>          DRG     HAD     2    0.024   1.0080  
>         [ bonds ]
>         ; ai  aj  fu    c0, c1, ...
>           2   1   2    0.125  13400000.0    0.125  13400000.0 ;     C
>          OXT     2   3   2    0.125  13400000.0    0.125  13400000.0 ;  
>           C    O     2   4   2    0.153   7150000.0    0.153   7150000.0
>         ;     C   CA     5   4   2    0.147   8710000.0    0.147  
>         8710000.0 ;     N   CA     5   6   2    0.147   8710000.0  
>          0.147   8710000.0 ;     N  CAG     5   7   2    0.134
>          10500000.0    0.134  10500000.0 ;     N  CAH     7   8   2  
>          0.134  10500000.0    0.134  10500000.0 ;   CAH  NAE     7  11  
>         2    0.134  10500000.0    0.134  10500000.0 ;   CAH  NAD     8  
>         9   2    0.100  18700000.0    0.100  18700000.0 ;   NAE  HA6    
>         8  10   2    0.100  18700000.0    0.100  18700000.0 ;   NAE  HAE
>            11  12   2    0.100  18700000.0    0.100  18700000.0 ;   NAD
>          HA5    11  13   2    0.100  18700000.0    0.100  18700000.0 ;  
>         NAD  HAD  
>         [ pairs ]
>         ; ai  aj  fu    c0, c1, ...
>           1   5   1                                           ;   OXT  
>          N     2   6   1                                           ;    
>         C  CAG     2   7   1                                           ;
>             C  CAH     3   5   1                                        
>           ;     O    N     4   8   1                                    
>               ;    CA  NAE     4  11   1                                
>                   ;    CA  NAD     5   9   1                            
>                       ;     N  HA6     5  10   1                        
>                           ;     N  HAE     5  12   1                    
>                               ;     N  HA5     5  13   1                
>                                   ;     N  HAD     6   8   1            
>                                       ;   CAG  NAE     6  11   1        
>                                           ;   CAG  NAD     8  12   1    
>                                               ;   NAE  HA5     8  13   1
>                                                   ;   NAE  HAD     9  11
>           1                                           ;   HA6  NAD    10
>          11   1                                           ;   HAE  NAD  
>         [ angles ]
>         ; ai  aj  ak  fu    c0, c1, ...
>           1   2   3   2    126.0       770.0    126.0       770.0 ;  
>         OXT    C    O     1   2   4   2    117.0       635.0    117.0  
>             635.0 ;   OXT    C   CA     3   2   4   2    117.0      
>         635.0    117.0       635.0 ;     O    C   CA     2   4   5   2  
>          109.5       520.0    109.5       520.0 ;     C   CA    N     4
>           5   6   2    121.0       685.0    121.0       685.0 ;    CA  
>          N  CAG     4   5   7   2    122.0       700.0    122.0      
>         700.0 ;    CA    N  CAH     6   5   7   2    117.0       635.0  
>          117.0       635.0 ;   CAG    N  CAH     5   7   8   2    120.0
>               670.0    120.0       670.0 ;     N  CAH  NAE     5   7  11
>           2    120.0       670.0    120.0       670.0 ;     N  CAH  NAD
>             8   7  11   2    120.0       670.0    120.0       670.0 ;  
>         NAE  CAH  NAD     7   8   9   2    120.0       390.0    120.0  
>             390.0 ;   CAH  NAE  HA6     7   8  10   2    120.0      
>         390.0    120.0       390.0 ;   CAH  NAE  HAE     9   8  10   2  
>          120.0       445.0    120.0       445.0 ;   HA6  NAE  HAE     7
>          11  12   2    120.0       390.0    120.0       390.0 ;   CAH
>          NAD  HA5     7  11  13   2    120.0       390.0    120.0      
>         390.0 ;   CAH  NAD  HAD    12  11  13   2    120.0       445.0  
>          120.0       445.0 ;   HA5  NAD  HAD  
>         [ dihedrals ]
>         ; ai  aj  ak  al  fu    c0, c1, m, ...
>           2   1   3   4   2      0.0  167.4        0.0  167.4   ; imp  
>           C  OXT    O   CA     5   4   6   7   2      0.0  167.4      
>          0.0  167.4   ; imp     N   CA  CAG  CAH     7   5   8  11   2  
>            0.0  167.4        0.0  167.4   ; imp   CAH    N  NAE  NAD    
>         8   7  10   9   2      0.0  167.4        0.0  167.4   ; imp  
>         NAE  CAH  HAE  HA6    11   7  13  12   2      0.0  167.4      
>          0.0  167.4   ; imp   NAD  CAH  HAD  HA5     5   4   2   1   1  
>            0.0    1.0 6      0.0    1.0 6 ; dih     N   CA    C  OXT    
>         2   4   5   7   1    180.0    1.0 6    180.0    1.0 6 ; dih    
>         C   CA    N  CAH    11   7   5   4   1    180.0   33.5 2  
>          180.0   33.5 2 ; dih   NAD  CAH    N   CA     5   7   8  10   1
>            180.0   33.5 2    180.0   33.5 2 ; dih     N  CAH  NAE  HAE  
>           5   7  11  13   1    180.0   33.5 2    180.0   33.5 2 ; dih  
>           N  CAH  NAD  HAD  
> 
> 
> 
> 
> 
> 
> 
>         *And top. I am prettu sure this file is wrong. And I do not know
>         yet how to modify it correctly:
> 
>         *
> 
>         ;
>         ;    File 'creatine.top' was generated
>         ;    By user: onbekend (0)
>         ;    On host: onbekend
>         ;    At date: Mon Nov 15 13:24:44 2010
>         ;
>         ;    This is your topology file
>         ;    it was generated using program:
>         ;    pdb2gmx - version 4.5-beta2
>         ;    with command line:
>         ;    pdb2gmx -f creatine_all_hyd_PRODRGBeta.pdb -o creatine.gro
>         -p creatine.top
>         ;
> 
>         #include "creatine.itp"
>         #include "gromos43a1.ff"
> 
> 
>         ; Include forcefield parameters
>         ;#include "gromos43a1.ff/forcefield.itp"
> 
>         ;"gromos43a1.ff/creatine.itp"
> 
> 
>         ;[ system ]
> 
>         ;[ molecules ]
>         ;DRG      3
> 
> 
> 
> 
>         2010/11/15 Vitaly Chaban <vvchaban at gmail.com
>         <mailto:vvchaban at gmail.com> <mailto:vvchaban at gmail.com
>         <mailto:vvchaban at gmail.com>>>
> 
> 
>            Hey, Olga -
> 
>             > Also please can you tell me where can I get "ffgmx.itp" file?
> 
>            /$gromacs_folder/share/gromacs/top/ffgmx.itp as well as all other
>            standard topology files are there.
> 
>            By trying to run md I am getting an error: Fatal error:
>             > moleculetype UNK is redefined
> 
>            Please post you top and itp files here. Looks like you have 2
>         creatine
>            molecules in your topology right now.
> 
>            Good luck!
> 
>            Vitaly
> 
> 
> 
> 
>             > I still have troubles of starting running md for creatine. For
>            which I
>             > created topology using PRODRG programm.
>             > The only difference between creatine.top and creating.itp
>         is that
>            creatine
>             > top has additional lines:
>             >  #include "ffgmx.itp"
>             > #include "creatine.itp"
>             >
>             > Also please can you tell me where can I get "ffgmx.itp" file?
>             >
>             > By trying to run md I am getting an error: Fatal error:
>             > moleculetype UNK is redefined
> 
> 
> 
>     -- 
>     ========================================
> 
>     Justin A. Lemkul
>     Ph.D. Candidate
>     ICTAS Doctoral Scholar
>     MILES-IGERT Trainee
>     Department of Biochemistry
>     Virginia Tech
>     Blacksburg, VA
>     jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
>     ========================================
> 
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> 

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

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
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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