[gmx-users] moleculaes breaking off after EM - help
Justin Lemkul
jalemkul at vt.edu
Wed Oct 5 15:24:12 CEST 2016
On 10/5/16 8:52 AM, Thejus Kartha wrote:
> 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?
>
These are all quantities that have to be calculated; you can't tell from a
topology what a hydration free energy is. Also don't use TIP4P for that
calculation; you need SPC.
Refer to the primary references for the GROMOS force field. You need to be
deriving parameters and validating them in a manner consistent with the parent
force field.
-Justin
>
> 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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