[gmx-users] Problems with Energy Minimization in Solvated Ligand

Fri Dec 29 23:42:46 CET 2017

On 12/29/17 5:14 PM, Toan Nguyen wrote:
> Is it okay to see this same warning when running npt and nvt?

No, hence the "IMPORTANT" part of the message. Your system is unstable 
and you should diagnose why.

http://www.gromacs.org/Documentation/Terminology/Blowing_Up#Diagnosing_an_Unstable_System

-Justin

> "*WARNING: Listed nonbonded interaction between particles 1 and 119*
> *at distance 2.103 which is larger than the table limit 2.000 nm.*
>
> *This is likely either a 1,4 interaction, or a listed interaction inside*
> *a smaller molecule you are decoupling during a free energy calculation.*
> *Since interactions at distances beyond the table cannot be computed,*
> *they are skipped until they are inside the table limit again. You will*
> *only see this message once, even if it occurs for several interactions.*
>
> *IMPORTANT: This should not happen in a stable simulation, so there is*
> *probably something wrong with your system. Only change the table-extension*
> *distance in the mdp file if you are really sure that is the reason."*
>
> On Thu, Dec 28, 2017 at 6:38 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>> On 12/28/17 9:36 PM, Toan Nguyen wrote:
>>
>>> How would we go about doing another energy minimization? I realized I sent
>>>
>> Double precision, or using conjugate gradients, or using steepest descents
>> with a smaller initial step.
>>
>> the wrong tutorial earlier, I was actually following this one Absolute
>>> Binding Free Energy - Gromacs 2016
>>> <http://www.alchemistry.org/wiki/Absolute_Binding_Free_Energ
>>> y_-_Gromacs_2016>
>>> by David Mobley.
>>>
>> Good luck getting that to converge with a peptide :)
>>
>> -Justin
>>
>>
>> On Thu, Dec 28, 2017 at 6:30 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>> On 12/28/17 8:40 PM, Toan Nguyen wrote:
>>>>
>>>> Hi,
>>>>> I am currently following the Gromacs Tutorial by Bevan Lab (Link
>>>>> <http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gm
>>>>> x-tutorials/complex/05_EM.html>)
>>>>> to run a simulation on a ligand from the 1mnb protein. However, I am
>>>>> running into issues with the energy minimization step where I run *gmx
>>>>> mdrun -v -nt 1 -deffnm em*, but an error arises saying,
>>>>>
>>>>> *"WARNING: Listed nonbonded interaction between particles 1 and 119*
>>>>> *at distance 2.108 which is larger than the table limit 2.000 nm.*
>>>>>
>>>>> *This is likely either a 1,4 interaction, or a listed interaction
>>>>> inside*
>>>>> *a smaller molecule you are decoupling during a free energy
>>>>> calculation.*
>>>>> *Since interactions at distances beyond the table cannot be computed,*
>>>>> *they are skipped until they are inside the table limit again. You will*
>>>>> *only see this message once, even if it occurs for several
>>>>> interactions.*
>>>>>
>>>>> *IMPORTANT: This should not happen in a stable simulation, so there is*
>>>>> *probably something wrong with your system. Only change the
>>>>> table-extension*
>>>>> *distance in the mdp file if you are really sure that is the reason."*
>>>>>
>>>>> and then energy minimization runs for ~120 steps before saying,
>>>>>
>>>>> *"Energy minimization has stopped, but the forces have not converged to
>>>>> the*
>>>>> *requested precision Fmax < 100 (which may not be possible for your
>>>>> system).*
>>>>> *It stopped because the algorithm tried to make a new step whose size
>>>>> was
>>>>> too*
>>>>> *small, or there was no change in the energy since last step. Either
>>>>> way,
>>>>> we*
>>>>> *regard the minimization as converged to within the available machine*
>>>>> *precision, given your starting configuration and EM parameters.*
>>>>>
>>>>> *Double precision normally gives you higher accuracy, but this is often
>>>>> not*
>>>>> *needed for preparing to run molecular dynamics.*
>>>>>
>>>>> *writing lowest energy coordinates.*
>>>>>
>>>>> *Steepest Descents converged to machine precision in 94 steps,*
>>>>> *but did not reach the requested Fmax < 100.*
>>>>> *Potential Energy  = -1.4016720e+05*
>>>>> *Maximum force     =  1.9569155e+03 on atom 259*
>>>>> *Norm of force     =  9.6724640e+01"*
>>>>>
>>>>> When I do the tutorial with the provided input files, this message does
>>>>> not
>>>>> show up and the energy minimization reaches 500+ steps. How can I fix my
>>>>> input files so that the energy minimization does not run into the
>>>>> problem
>>>>> above?
>>>>>
>>>>> Below is the link to my input files:
>>>>> Link
>>>>> <https://drive.google.com/drive/folders/1a38C0lnBWi6n1IfalGU
>>>>> -SKc0_cnxBRqa?usp=sharing>
>>>>>
>>>>> The messages above just indicate you probably have a bad contact
>>>> somewhere
>>>> early on in the minimization process. If EM finishes (which it does),
>>>> then
>>>> the bad contact has been at least somewhat resolved. The forces are still
>>>> somewhat high, so you will likely need additional minimization and/or
>>>> double precision, as the message from mdrun suggests.
>>>>
>>>> The protein-ligand complex tutorial isn't really relevant here; you just
>>>> have a very simple protein in water, not that it makes much difference.
>>>> But
>>>> don't get too hung up on having a "ligand" in your system. You have a
>>>> peptide, so it's nothing that requires any really special procedur
>>>> <https://maps.google.com/?q=that+requires+any+really+special+procedur&entry=gmail&source=g>
>>>> e.
>>>>
>>>> -Justin
>>>>
>>>> --
>>>> ==================================================
>>>>
>>>> Justin A. Lemkul, Ph.D.
>>>> Assistant Professor
>>>> Virginia Tech Department of Biochemistry
>>>>
>>>> 303 Engel Hall
>>>> 340 West Campus Dr.
>>>> Blacksburg, VA 24061
>>>>
>>>> jalemkul at vt.edu | (540) 231-3129
>>>> http://www.biochem.vt.edu/people/faculty/JustinLemkul.html
>>>>
>>>> ==================================================
>>>>
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>>>>
>>>
>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Assistant Professor
>> Virginia Tech Department of Biochemistry
>>
>> 303 Engel Hall
>> 340 West Campus Dr.
>> Blacksburg, VA 24061
>>
>> jalemkul at vt.edu | (540) 231-3129
>> http://www.biochem.vt.edu/people/faculty/JustinLemkul.html
>>
>> ==================================================
>>
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>> Gromacs Users mailing list
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>
>

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

Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

303 Engel Hall
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129
http://www.biochem.vt.edu/people/faculty/JustinLemkul.html

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