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

[Justin Lemkul]

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/gmx-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

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

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