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

Justin Lemkul jalemkul at vt.edu
Wed Oct 5 14:30:56 CEST 2016



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
> ;
> ;       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> 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 | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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


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