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

[Justin Lemkul]

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_Energy_-_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 procedure.
>>
>> -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

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