# Error during energy minimization

**URL:** <https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767>\
**Category:** User discussions\
**Tags:** mdrun, energy-minization, pmx\
**Created:** [March 18, 2025, 11:31am UTC](https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767 "2025-03-18T11:31:34Z")\
**Posts on this page:** 5\
**Page:** 1

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**Author:** ![AntonBer](https://avatars.discourse-cdn.com/v4/letter/a/6de8d8/32.png) [@AntonBer](https://gromacs.bioexcel.eu/u/AntonBer)\
**Post date:** [March 18, 2025, 11:31am UTC](https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767/1 "2025-03-18T11:31:34Z")

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GROMACS version: 2025.0  
GROMACS modification: No  
pmx version: 0+untagged.888.g09b57c6

Hello,  
I’m currently trying to setup and perform ABFE calculations using GROMACS and PMX. During energy minimization for lambda=0 (same error for lambda=1) I got error:

```auto
Fatal error:
There are 2 perturbed, excluded non-bonded pair interactions beyond the
pair-list cut-off, which is not supported. This can happen because the system
is unstable or because intra-molecular interactions at long distances are
excluded. If the latter is the case, you can try to increase nstlist or rlist
to avoid this.The error is likely triggered by the use of couple-intramol=no
and the maximal distance in the decoupled molecule exceeding rlist.

```

How can I solve this error?  
nstlist/rlist increase doesn’t help.  
Attached mdp file and topology.  
I can attach link to coordinates file if it helps with google drive.

[em\_l0.mdp](https://gromacs.bioexcel.eu/uploads/short-url/77wknMYPHp9rq7pp6xoh9rSs7KI.mdp) (7.6 KB)  
[ligand.top](https://gromacs.bioexcel.eu/uploads/short-url/yn5AY2Hq292UGHUBH5eAnWWoBAN.top) (24.2 KB)

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<div class="post-metadata">

**Author:** ![hess](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/hess/32/416_2.png) [@hess](https://gromacs.bioexcel.eu/u/hess)\
**Post date:** [March 19, 2025, 2:58pm UTC](https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767/2 "2025-03-19T14:58:08Z")

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Use couple-intramol=yes and add a vacuum leg to your calculation. If the maximum distance is close to rlist you can consider increasing rlist instead.

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<div class="post-metadata">

**Author:** ![AntonBer](https://avatars.discourse-cdn.com/v4/letter/a/6de8d8/32.png) [@AntonBer](https://gromacs.bioexcel.eu/u/AntonBer)\
**Post date:** [April 11, 2025, 3:13pm UTC](https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767/3 "2025-04-11T15:13:29Z")

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Thanks for your answer. Could you please describe what do you mean by “vacuum leg”? As far as I know vacuum simulations currently not supported in GROMACS.

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<div class="post-metadata">

**Author:** ![hess](https://dub1.discourse-cdn.com/flex017/user_avatar/gromacs.bioexcel.eu/hess/32/416_2.png) [@hess](https://gromacs.bioexcel.eu/u/hess)\
**Post date:** [April 14, 2025, 1:38pm UTC](https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767/4 "2025-04-14T13:38:21Z")

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You need to compute the cost of (de)coupling the molecule in vacuum. You remove the solvent from the system, keep the same box and run exactly the same calculations as for the solvent case.

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<div class="post-metadata">

**Author:** ![AntonBer](https://avatars.discourse-cdn.com/v4/letter/a/6de8d8/32.png) [@AntonBer](https://gromacs.bioexcel.eu/u/AntonBer)\
**Post date:** [April 15, 2025, 1:56pm UTC](https://gromacs.bioexcel.eu/t/error-during-energy-minimization/11767/5 "2025-04-15T13:56:52Z")

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Thank you!