[gmx-users] Polar Hydrogen missing using PRODRG

Justin A. Lemkul jalemkul at vt.edu
Thu Oct 14 14:01:10 CEST 2010



Jennifer Williams wrote:
> 
> Hi,
> 
> So, I did as suggested. Ran PRODRG the first time using the JME Editor 
> and took the pdb file from this. Then I added the ADDHYD OAE underneath 
> (actually it doesn't matter which O (OAD or OAE) is protonated as long 
> as it is only one of them).
> 
> The first bit of output looked encouraging...
> 
> PRODRG> PDB mode detected.
> PRODRG> Molecule complexity index: 2.00.
> PRODRG> Added hydrogen on atom OAE .
> PRODRG>  18 hydrogen(s) added.
> PRODRG> Using charge groups.
> PRODRG> Net charge on molecule:   0.000
> PRODRG>  20 partial charges      0 ambiguous
> PRODRG> Cannot assign type to atom ' OAE'.
> ERRDRG> Error in GROMOS atom names/types.
> PRODRG> Program terminated unsuccessfully, sorry!
> 
> So it understood that I wanted a hydrogen and the net charge is at last 
> 0(usually -1 without that hydrogen) but then it crashes! I don't 
> understand why it can't assign a type to OAE. IS it because a hydrogen 
> is now attached so the hybridisation has changed from sp2 to sp3?
> 
> Do I need to change the identity of OAE before putting a hydrogen on? If 
> so to what?
> 

It looks like PRODRG simply isn't working as advertised.  I can force 
protonation of N atoms without problem, but it won't work for O for some reason. 
    You have several options:

1. Write an .rtp entry for your molecule instead.
2. Add the H in manually and add the bonded parameters for it.  Since PRODRG 
charges have to be manually changed anyway, this isn't too much more work.

-Justin

> Thanks
> 
> Jenny
> 
> 
> REMARK
> REMARK
> REMARK  This file was generated by PRODRG version 071121.0636
> REMARK  PRODRG written/copyrighted by Daan van Aalten
> REMARK  and Alexander Schuettelkopf
> REMARK
> REMARK  Questions/comments to dava at davapc1.bioch.dundee.ac.uk
> REMARK
> REMARK  When using this software in a publication, cite:
> REMARK  A. W. Schuettelkopf and D. M. F. van Aalten (2004).
> REMARK  PRODRG - a tool for high-throughput crystallography
> REMARK  of protein-ligand complexes.
> REMARK  Acta Crystallogr. D60, 1355--1363.
> REMARK
> REMARK
> HETATM    1  CAA DRG     1       2.360   1.610   1.840  1.00 20.00     
>         C
> HETATM    2  CAN DRG     1       3.580   2.340   1.260  1.00 20.00     
>         C
> HETATM    3  CAB DRG     1       3.330   2.650  -0.210  1.00 20.00     
>         C
> HETATM    4  CAJ DRG     1       4.820   1.450   1.460  1.00 20.00     
>         C
> HETATM    5  CAL DRG     1       6.160   2.130   1.140  1.00 20.00     
>         C
> HETATM    6  CAG DRG     1       6.870   1.740  -0.010  1.00 20.00     
>         C
> HETATM    7  CAI DRG     1       8.100   2.360  -0.300  1.00 20.00     
>         C
> HETATM    8  CAF DRG     1       6.640   3.140   2.010  1.00 20.00     
>         C
> HETATM    9  CAH DRG     1       7.870   3.760   1.720  1.00 20.00     
>         C
> HETATM   10  CAM DRG     1       8.600   3.370   0.570  1.00 20.00     
>         C
> HETATM   11  CAO DRG     1       9.930   4.110   0.310  1.00 20.00     
>         C
> HETATM   12  CAC DRG     1      10.120   4.580  -1.140  1.00 20.00     
>         C
> HETATM   13  CAK DRG     1      11.150   3.250   0.700  1.00 20.00     
>         C
> HETATM   14  OAE DRG     1      12.100   3.870   1.240  1.00 20.00     
>         O
> HETATM   15  OAD DRG     1      11.130   2.020   0.480  1.00 20.00     
>         O
> CONECT    1    2
> CONECT    2    1    3    4
> CONECT    3    2
> CONECT    4    2    5
> CONECT    5    4    6    8
> CONECT    6    5    7
> CONECT    7    6   10
> CONECT    8    5    9
> CONECT    9    8   10
> CONECT   10    7    9   11
> CONECT   11   10   12   13
> CONECT   12   11
> CONECT   13   11   14   15
> CONECT   14   13
> CONECT   15   13
> END
> ADDHYD OAE
> 
> 
> 
> 
> 
> 
> 
> 
> Quoting "Justin A. Lemkul" <jalemkul at vt.edu>:
> 
>>
>> You need to run PRODRG twice.  The first time, do not use ADDHYD.  Make
>> note of the atom names that PRODRG assigns.  Then run PRODRG a second
>> time, using ADDHYD with the atom name that PRODRG uses for the O atom
>> you want protonated.
>>
>> -Justin
>>
>> Jennifer Williams wrote:
>>>
>>>
>>> Hi Justin,
>>>
>>> Thanks for your answer. The ADDHYD in the FAQ sounds like exactly  
>>> what I need however I can't get this command to work. I draw in my  
>>> molecule using the JME editor and get this .pdb file in the PRODRG  
>>> window.
>>>
>>> CC(C)Cc1ccc(C(C)C(=O)O)cc1
>>> JME 2002.05 Thu Oct 14 10:48:38 BST 2010
>>>
>>> 15 15                            V2000
>>>    0.0000    0.0000    0.0000 C
>>>    1.2124    2.1000    0.0000 C
>>>    7.2746    4.2000    0.0000 C
>>>    8.4870    0.7000    0.0000 O
>>>    9.6995    2.8000    0.0000 O
>>>    3.6373    2.1000    0.0000 C
>>>    4.8497    0.0000    0.0000 C
>>>    4.8497    2.8000    0.0000 C
>>>    6.0622    0.7000    0.0000 C
>>>    2.4249    0.0000    0.0000 C
>>>    8.4870    2.1000    0.0000 C
>>>    3.6373    0.7000    0.0000 C
>>>    6.0622    2.1000    0.0000 C
>>>    1.2124    0.7000    0.0000 C
>>>    7.2746    2.8000    0.0000 C
>>>  1 14  1  0
>>>  2 14  1  0
>>>  3 15  1  0
>>>  4 11  2  0
>>>  5 11  1  0
>>>  6  8  1  0
>>>  6 12  2  0
>>>  7  9  2  0
>>>  7 12  1  0
>>>  8 13  2  0
>>>  9 13  1  0
>>> 10 12  1  0
>>> 10 14  1  0
>>> 11 15  1  0
>>> 13 15  1  0
>>> M  END
>>>
>>> If I then try adding ADDHYD O to the window and clicking "run  
>>> PRODRG" I get the following:
>>>
>>> ERRDRG> Atom 'O' referenced in instruction was not found.
>>> PRODRG> Program terminated unsuccessfully, sorry!
>>>
>>> I've then tried renaming O to OM as there are 2 Os in my structure  
>>> and I only want one protonated. However, no other name is  recognized 
>>> so I get this message:
>>>
>>> ERRDRG> Currently only N, C, O, S, P, Cl, Br, F, I are supported.
>>> PRODRG> Program terminated unsuccessfully, sorry!
>>>
>>> Next I tried using the PDB generated by PRODRG and repasting it  with 
>>> the ADDHYD command into the PRODRG window.
>>>
>>> Now the pdb looks like this:
>>>
>>> REMARK
>>> REMARK
>>> REMARK  This file was generated by PRODRG version 071121.0636
>>> REMARK  PRODRG written/copyrighted by Daan van Aalten
>>> REMARK  and Alexander Schuettelkopf
>>> REMARK
>>> REMARK  Questions/comments to dava at davapc1.bioch.dundee.ac.uk
>>> REMARK
>>> REMARK  When using this software in a publication, cite:
>>> REMARK  A. W. Schuettelkopf and D. M. F. van Aalten (2004).
>>> REMARK  PRODRG - a tool for high-throughput crystallography
>>> REMARK  of protein-ligand complexes.
>>> REMARK  Acta Crystallogr. D60, 1355--1363.
>>> REMARK
>>> REMARK
>>> HETATM    1  CAA DRG     1       2.360   1.610   1.840  1.00 20.00  
>>>            C
>>> HETATM    2  CAN DRG     1       3.580   2.340   1.260  1.00 20.00  
>>>            C
>>> HETATM    3  CAB DRG     1       3.330   2.650  -0.210  1.00 20.00  
>>>            C
>>> HETATM    4  CAJ DRG     1       4.820   1.450   1.460  1.00 20.00  
>>>            C
>>> HETATM    5  CAL DRG     1       6.160   2.130   1.140  1.00 20.00  
>>>            C
>>> HETATM    6  CAG DRG     1       6.870   1.740  -0.010  1.00 20.00  
>>>            C
>>> HETATM    7  CAI DRG     1       8.100   2.360  -0.300  1.00 20.00  
>>>            C
>>> HETATM    8  CAF DRG     1       6.640   3.140   2.010  1.00 20.00  
>>>            C
>>> HETATM    9  CAH DRG     1       7.870   3.760   1.720  1.00 20.00  
>>>            C
>>> HETATM   10  CAM DRG     1       8.600   3.370   0.570  1.00 20.00  
>>>            C
>>> HETATM   11  CAO DRG     1       9.930   4.110   0.310  1.00 20.00  
>>>            C
>>> HETATM   12  CAC DRG     1      10.120   4.580  -1.140  1.00 20.00  
>>>            C
>>> HETATM   13  CAK DRG     1      11.150   3.250   0.700  1.00 20.00  
>>>            C
>>> HETATM   14  OAE DRG     1      12.100   3.870   1.240  1.00 20.00  
>>>            O
>>> HETATM   15  OAD DRG     1      11.130   2.020   0.480  1.00 20.00  
>>>            O
>>> CONECT    1    2
>>> CONECT    2    1    3    4
>>> CONECT    3    2
>>> CONECT    4    2    5
>>> CONECT    5    4    6    8
>>> CONECT    6    5    7
>>> CONECT    7    6   10
>>> CONECT    8    5    9
>>> CONECT    9    8   10
>>> CONECT   10    7    9   11
>>> CONECT   11   10   12   13
>>> CONECT   12   11
>>> CONECT   13   11   14   15
>>> CONECT   14   13
>>> CONECT   15   13
>>> END
>>>
>>> I've tried changing the HETATM to OM and using ADDHYD OM and then  
>>> played around with various other things like renaming the atom  
>>> symbol at the end of the line and even the OAD, DRG but I always  get 
>>> the following:
>>>
>>> ERRDRG> Atom 'OM' referenced in instruction was not found.
>>> PRODRG> Program terminated unsuccessfully, sorry!
>>>
>>> I am using the PRODRG beta server available online at
>>>
>>> http://davapc1.bioch.dundee.ac.uk/cgi-bin/prodrg_beta
>>>
>>> Will I fare any better if I use the source code or is there  
>>> something obvious I am doing wrong? Does the ADDHYD have to be  added 
>>> in any particular location of the pdb file? I have tried a  few 
>>> random positions including at the very top, very bottom and  just 
>>> beneath the O to be protonated. Nothing worked.
>>>
>>> Any ideas much appreciated,
>>>
>>> Jenny
>>>
>>>
>>>
>>> Quoting "Justin A. Lemkul" <jalemkul at vt.edu>:
>>>
>>>>
>>>>
>>>> Jennifer Williams wrote:
>>>>>
>>>>>
>>>>> Hi,
>>>>>
>>>>> I am trying to get a .itp file for a simple molecule (Ibuprofen).   
>>>>> This contains a COOH group.
>>>>>
>>>>> THe problem is that PRODRG removes the polar hydrogen of the COOH   
>>>>> from the .pdb file and generates a .itp file without it.
>>>>>
>>>>> I am not concerned about the other aromatic hydrogens but I  
>>>>> really  need the polar hydrogen modelled explicitly.
>>>>>
>>>>> Is there a fix for this within PRODRG?
>>>>>
>>>>> I know I can use pdb2gmx to add hydrogens but the residue names  
>>>>> of  the pdb file are not recognized by the existing forcefields  so 
>>>>> I  usually bypass using pdb2gmx.
>>>>>
>>>>>
>>>>
>>>> Have a look at the PRODRG FAQ - there's an entry there for modifying
>>>> protonation state.
>>>>
>>>> -Justin
>>>>
>>>>> Thanks
>>>>>
>>>>> Jenny
>>>>>
>>>>>
>>>>>
>>>>> Dr. Jennifer Williams
>>>>> Institute for Materials and Processes
>>>>> School of Engineering
>>>>> University of Edinburgh
>>>>> Sanderson Building
>>>>> The King's Buildings
>>>>> Mayfield Road
>>>>> Edinburgh, EH9 3JL, United Kingdom
>>>>> Phone: ++44 (0)131 650 4 861
>>>>>
>>>>>
>>>>
>>>> -- 
>>>> ========================================
>>>>
>>>> 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
>>>>
>>>> ========================================
>>>> -- 
>>>> gmx-users mailing list    gmx-users at gromacs.org
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>>>> Please search the archive at
>>>> http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
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>>>
>>>
>>>
>>> Dr. Jennifer Williams
>>> Institute for Materials and Processes
>>> School of Engineering
>>> University of Edinburgh
>>> Sanderson Building
>>> The King's Buildings
>>> Mayfield Road
>>> Edinburgh, EH9 3JL, United Kingdom
>>> Phone: ++44 (0)131 650 4 861
>>>
>>>
>>
>> -- 
>> ========================================
>>
>> 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
>>
>> ========================================
>> -- 
>> gmx-users mailing list    gmx-users at gromacs.org
>> http://lists.gromacs.org/mailman/listinfo/gmx-users
>> Please search the archive at
>> http://www.gromacs.org/Support/Mailing_Lists/Search before posting!
>> Please don't post (un)subscribe requests to the list. Use the www
>> interface or send it to gmx-users-request at gromacs.org.
>> Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> 
> 
> 
> Dr. Jennifer Williams
> Institute for Materials and Processes
> School of Engineering
> University of Edinburgh
> Sanderson Building
> The King's Buildings
> Mayfield Road
> Edinburgh, EH9 3JL, United Kingdom
> Phone: ++44 (0)131 650 4 861
> 
> 

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

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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