[gmx-users] moleculaes breaking off after EM - help

Thejus Kartha thejuskartha at ymail.com
Wed Oct 5 15:21:11 CEST 2016


I'm certain that I am creating a box of 512 molecules appropriately. I use the gmx genconf command to do it, and a VMD visualization of that looks perfectly okay. But, it starts to break off only after I perform an energy minimization on it. So, the next thing on my list would be to look at my topology more closely, and what am I to look for here? I mean, what part of the topology reflects my hydration free energy, or any other material property for that matter?
 

    On Wednesday, 5 October 2016 6:11 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
 

 

On 10/5/16 8:37 AM, Thejus Kartha wrote:
> Interestingly, the in vacuo test with a single molecule went well. No molecule
> breaking off there. Energy minimized well. In fact a bit too well - I ran a
> preliminary steepest descent minimization in Avogadro which gave my potential
> value to be about 112 kJ/mol for a single molecule. Gromacs brought it down
> further to 31.6 kJ/mol. And I repeat, dioxane remained intact.
>

Then there are two possibilities:

1. The dioxane topology is inappropriate for describing intermolecular 
interactions in the condensed phase
2. The initial coordinates were simply bad and caused a crash

Validating the topology against known target data (QM dipole moment, hydration 
free energy, etc) is the first step.  The second is making sure you correctly 
build a box of 512 molecules.

-Justin

>
> On Wednesday, 5 October 2016 6:00 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>
>
>
> On 10/5/16 12:11 AM, Thejus Kartha wrote:
>> Thanks, Dr. Lemkul, for your assistance. Here's my topology file, for 512
> atoms. Please tell me where I'm going wrong in this. Frankly, I can't find
> issues with this, even after comparing it with any other topology file created
> by GROMACS itself. Please go through it and let me
> know.--------------------------------Topology
> file------------------------------------------------------------
>> ;
>> ;
>> ;      This file was generated by PRODRG version AA100323.0717
>> ;      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>
>> ;
>> ;      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.
>> ;
>> ;
>>
>> ; Include forcefield parameters
>> #include "gromos43a1.ff/forcefield.itp"
>>
>> [ moleculetype ]
>> ; Name nrexcl
>> LIG      3
>>
>> [ atoms ]
>> ;  nr      type  resnr resid  atom  cgnr  charge    mass
>>      1      CH1    1  LIG    CAA    1    0.070  14.0270
>>      2        OA    1  LIG    OAB    1  -0.140  15.9994
>>      3      CH1    1  LIG    CAC    1    0.070  14.0270
>>      4      CH1    1  LIG    CAD    1    0.070  14.0270
>>      5        OA    1  LIG    OAE    1  -0.140  15.9994
>>      6      CH1    1  LIG    CAF    1    0.070  14.0270
>>
>
> For dioxane, the atom types for the carbons should all be CH2.  I can't vouch
> for the charges, but you should validate the topology based on available target
> data, e.g. free energy of hydration before proceeding.
>
> Otherwise, what I said before remains valid - do the in vacuo test.  If that
> works, then whatever you did to the coordinates for the condensed phase system
> was bad.
>
> -Justin
>
>
>> [ bonds ]
>> ; ai  aj  fu    c0, c1, ...
>>    1  2  2    0.144  6100000.0    0.144  6100000.0 ;  CAA  OAB
>>    1  6  2    0.152  5430000.0    0.152  5430000.0 ;  CAA  CAF
>>    3  2  2    0.144  6100000.0    0.144  6100000.0 ;  CAC  OAB
>>    3  4  2    0.152  5430000.0    0.152  5430000.0 ;  CAC  CAD
>>    4  5  2    0.144  6100000.0    0.144  6100000.0 ;  CAD  OAE
>>    6  5  2    0.144  6100000.0    0.144  6100000.0 ;  CAF  OAE
>>
>> [ pairs ]
>> ; ai  aj  fu    c0, c1, ...
>>    1  4  1                                          ;  CAA  CAD
>>    2  5  1                                          ;  OAB  OAE
>>    3  6  1                                          ;  CAC  CAF
>>
>> [ angles ]
>> ; ai  aj  ak  fu    c0, c1, ...
>>    2  1  6  2    109.5      520.0    109.5      520.0 ;  OAB  CAA  CAF
>>    1  2  3  2    109.5      380.0    109.5      380.0 ;  CAA  OAB  CAC
>>    2  3  4  2    109.5      520.0    109.5      520.0 ;  OAB  CAC  CAD
>>    3  4  5  2    109.5      520.0    109.5      520.0 ;  CAC  CAD  OAE
>>    4  5  6  2    109.5      380.0    109.5      380.0 ;  CAD  OAE  CAF
>>    1  6  5  2    109.5      520.0    109.5      520.0 ;  CAA  CAF  OAE
>>
>> [ dihedrals ]
>> ; ai  aj  ak  al  fu    c0, c1, m, ...
>>    6  1  2  3  1      0.0    3.8 3      0.0    3.8 3 ; dih  CAF  CAA  OAB  CAC
>>    5  6  1  2  1      0.0    5.9 3      0.0    5.9 3 ; dih  OAE  CAF  CAA  OAB
>>    4  3  2  1  1      0.0    3.8 3      0.0    3.8 3 ; dih  CAD  CAC  OAB  CAA
>>    5  4  3  2  1      0.0    5.9 3      0.0    5.9 3 ; dih  OAE  CAD  CAC  OAB
>>    3  4  5  6  1      0.0    3.8 3      0.0    3.8 3 ; dih  CAC  CAD  OAE  CAF
>>    1  6  5  4  1      0.0    3.8 3      0.0    3.8 3 ; dih  CAA  CAF  OAE  CAD
>>
>> ; Include Position restraint file
>> #ifdef POSRES
>> #include "posre.itp"
>> #endif
>>
>> ; Include water topology
>> #include "gromos43a1.ff/tip4p.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 "gromos43a1.ff/ions.itp"
>>
>> [ system ]
>> ; Name
>> Dioxane_10%
>>
>> [ molecules ]
>> ; Compound        #mols
>> LIG
> 512-----------------------------------------------------------------------------------------------------------------
>>
>> If you can't find anything wrong with it, I guess I should redo my genconf
> command. Isn't it?
>> Thanks & regards,Thejus Kartha
>>
>>
>>    On Monday, 3 October 2016 5:06 PM, Justin Lemkul <jalemkul at vt.edu
> <mailto:jalemkul at vt.edu>> wrote:
>>
>>
>>
>>
>> On 10/2/16 10:09 PM, Thejus Kartha wrote:
>>> Greetings!
>>> I was performing an EM run with an array of dioxane molecules, for which I
> had produced co-ordinates from PRODRG. I got the co-ordinates, and made an array
> of it, using the gmx genconf module, and corrected my topology file. Then, I
> thought I should minimize the energy of this array before solvating it, or
> anything. So, as I was running the grompp module using mdp files from Dr.
> Lemkul's tutorials, it gave me the following error:
>>> Steepest Descents converged to machine precision in 641 steps,
>>> but did not reach the requested Fmax < 1000.
>>> Potential Energy  =  2.6059185e+09
>>> Maximum force    =  8.6477500e+04 on atom 557
>>> Norm of force    =  7.7685435e+03
>>>
>>> I am presuming there's something seriously wrong with my input files, as I've
> been told many times before. That said, how do I tweak around with my mdp file
> in this case? I mean, there's this Fmax value that I have to deal with. How do I
> know if I am using the right threshold for Fmax? Do I base this value on
> information from literature? And of course, when I open the .gro file after the
> EM, I find my molecules to be smashed to smithereens. There are points and
> broken triangles flying around in all directions (dioxane is a hexagon, and it
> has broken to half.) Why does this happen? Please help me.
>>
>> This suggests your topology is wrong.  Test with one molecule in vacuo.  If it
>> does the same thing, fix the topology.  If the in vacuo test goes well, then
>> your coordinates in the assembled box are unreasonable.
>>
>> -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 <mailto:jalemkul at outerbanks.umaryland.edu> |
> (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
>
>

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

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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