MD crashes

[VesperChen01]

I have 10 molecules, and three or four of them have anomalies. However, during the topological and related processes, the parameter settings are the same for all molecules. Due to structural anomalies in some molecules (as shown in the figure, where the benzene ring should be normal), it leads to 'segmentation fault (MD crashes)' during the 'runall.sh' step.

[xy21hb]

I Guess you used Pymol "Add H" in the "Builder" panel to add H's for your molecule, so check your true protonation state very carefully before generating topologies.

[luancarvalhomartins]

The PDB that is passed to GROMACS contains atoms of both topologies A and B. PyMol assigns bond based on the distance between atoms, regardless of which of the topologies A and B they belong to. Therefore, what you are seeing is an artifact of the PyMol representation.

Are you observing segmentation faults in GROMACS or is your system blowing up? In the later case, double check the MCS between the molecules and the number of perturbed atoms. In case everything seems fine, try running using more lambda windows.

[VesperChen01]

1. This is 'feprun_133410_03082023.log'.

Step 12452, time 24.904 (ps) LINCS WARNING in simulation 1 relative constraint deviation after LINCS: rms 0.071517, max 2.333266 (between atoms 3684 and 3685) bonds that rotated more than 30 degrees: atom 1 atom 2 angle previous, current, constraint length 3684 3685 90.0 0.1080 0.3600 0.1080 4089 4076 90.0 0.1090 0.3521 0.1090 4089 4076 90.0 0.1090 0.3521 0.1090 4089 4076 90.0 0.1090 0.3521 0.1090 4089 4076 90.0 0.1090 0.3521 0.1090 4089 4076 90.0 0.1090 0.3521 0.1090 4089 4076 90.0 0.1090 0.3521 0.1090 4089 4076 90.0 0.1090 0.3521 0.1090

step 12400, will finish Thu Aug 3 17:36:16 2023Wrote pdb files with previous and current coordinates

Step 12453, time 24.906 (ps) LINCS WARNING in simulation 1 relative constraint deviation after LINCS: rms 0.856589, max 32.602646 (between atoms 3684 and 3685) bonds that rotated more than 30 degrees: atom 1 atom 2 angle previous, current, constraint length 3678 3679 90.0 0.1090 2.3710 0.1090 3680 3681 41.1 0.1090 0.1089 0.1090 3680 3682 90.0 0.1090 0.2196 0.1090 3684 3685 90.0 0.3600 3.6291 0.1080 4089 4076 62.9 0.3521 0.1088 0.1090 4089 4076 62.9 0.3521 0.1088 0.1090 4089 4076 62.9 0.3521 0.1088 0.1090 4089 4076 62.9 0.3521 0.1088 0.1090 4089 4076 62.9 0.3521 0.1088 0.1090 4089 4076 62.9 0.3521 0.1088 0.1090 4089 4076 62.9 0.3521 0.1088 0.1090 Wrote pdb files with previous and current coordinates

Step 12454, time 24.908 (ps) LINCS WARNING in simulation 1 relative constraint deviation after LINCS: rms 155306.125000, max 4049294.750000 (between atoms 926 and 927) bonds that rotated more than 30 degrees: atom 1 atom 2 angle previous, current, constraint length 924 925 55.0 0.1090 0.1090 0.1090 926 927 48.2 0.1090 441373.2188 0.1090 926 928 63.9 0.1090 440992.7188 0.1090 3678 3679 168.9 2.3710 440973.5625 0.1090 3680 3681 90.0 0.1089 0.1479 0.1090 3680 3682 81.6 0.2196 0.1045 0.1090 3684 3685 128.4 3.6291 8.2821 0.1080 4089 4076 90.0 0.1088 0.3150 0.1090 4089 4076 90.0 0.1088 0.3150 0.1090 4089 4076 90.0 0.1088 0.3150 0.1090 4089 4076 90.0 0.1088 0.3150 0.1090 4089 4076 90.0 0.1088 0.3150 0.1090 4089 4076 90.0 0.1088 0.3150 0.1090 4089 4076 90.0 0.1088 0.3150 0.1090 Wrote pdb files with previous and current coordinates

Step 12455, time 24.91 (ps) LINCS WARNING in simulation 1 relative constraint deviation after LINCS: rms 310620.750000, max 8098798.000000 (between atoms 926 and 927) bonds that rotated more than 30 degrees: atom 1 atom 2 angle previous, current, constraint length 924 925 90.0 0.1090 0.1254 0.1090 929 930 90.0 0.1090 0.1597 0.1090 929 931 90.0 0.1090 0.1512 0.1090 3676 3677 90.0 0.1010 0.4017 0.1010 3680 3681 109.9 0.1479 32.9508 0.1090 3680 3682 133.1 0.1045 32.1523 0.1090 3690 3691 96.0 0.1080 29.0857 0.1080 4089 4076 64.3 0.3150 0.1089 0.1090 4089 4076 64.3 0.3150 0.1089 0.1090 4089 4076 64.3 0.3150 0.1089 0.1090 4089 4076 64.3 0.3150 0.1089 0.1090 4089 4076 64.3 0.3150 0.1089 0.1090 4089 4076 64.3 0.3150 0.1089 0.1090 4089 4076 64.3 0.3150 0.1089 0.1090

step 12500, will finish Thu Aug 3 17:35:59 2023Wrote pdb files with previous and current coordinates

Step 12456, time 24.912 (ps) LINCS WARNING in simulation 1 relative constraint deviation after LINCS: rms 470287.593750, max 12148295.000000 (between atoms 926 and 927) bonds that rotated more than 30 degrees: atom 1 atom 2 angle previous, current, constraint length 658 659 90.0 0.1090 1.4800 0.1090 658 660 35.6 0.1090 0.1131 0.1090 924 925 90.0 0.1254 4.5405 0.1090 929 930 90.0 0.1597 0.1821 0.1090 929 931 90.0 0.1512 0.1524 0.1090 1676 1677 147.3 0.1090 1724.5902 0.1090 2059 2060 90.0 0.1090 0.2767 0.1090 2059 2061 90.0 0.1090 0.2799 0.1090 2059 2062 144.4 0.1090 171431.3906 0.1090 3574 3575 90.0 0.1090 3.2540 0.1090 3647 3648 75.0 0.1010 18657.6113 0.1010 3649 3650 90.0 0.1090 0.2782 0.1090 3649 3651 90.0 0.1090 0.2322 0.1090 3668 3669 90.0 0.1090 0.3968 0.1090 3676 3677 116.6 0.4017 12313.8086 0.1010 3680 3682 113.1 32.1523 1701.8857 0.1090 3686 3687 90.0 0.1080 0.2152 0.1080 3688 3689 90.0 0.1080 0.1184 0.1080 3690 3691 110.9 29.0857 259555.5000 0.1080 3693 3694 90.0 0.0945 0.4423 0.0945 3719 3720 98.8 0.1010 3540.3989 0.1010 3721 3722 90.0 0.1090 0.1695 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090 4089 4076 90.0 0.1089 0.3025 0.1090

step 12456: One or more water molecules can not be settled. Check for bad contacts and/or reduce the timestep if appropriate. Wrote pdb files with previous and current coordinates [DESKTOP-FV9G3UP:162792] Process received signal [DESKTOP-FV9G3UP:162792] Signal: Segmentation fault (11) [DESKTOP-FV9G3UP:162792] Signal code: Address not mapped (1) [DESKTOP-FV9G3UP:162792] Failing at address: 0x55ed2f4b2608

Primary job terminated normally, but 1 process returned a non-zero exit code. Per user-direction, the job has been aborted.

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

step 12600, will finish Thu Aug 3 17:35:53 2023 step 12700, will finish Thu Aug 3 17:35:39 2023

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

Received the TERM signal, stopping within 100 steps

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mpirun noticed that process rank 1 with PID 0 on node DESKTOP-FV9G3UP exited on signal 11 (Segmentation fault).

2. Many pdb files have been generated in the path tutorial/C-7-d-9/protein/md/lambda1/.

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I may not fully understand the script, please provide me with more detailed questions and solutions. If it's too concise, I may not be able to comprehend it. Thank you!

@luancarvalhomartins

[xy21hb]

the system seemingly is not properly energy minimized. All those step1245*.pdbs are GROMACS intermediate files. So check your system carefully, esp. solvation and try to run longer minimization and LINCS_order in your em.mdp.

[luancarvalhomartins]

Your system is blowing up.

1. Is your topology correct? Make sure to check, as this is the most likely problem.
   • Also check the MCS and the perturbed region, make sure it is correct.
2. In case everything is fine, you may try:
   • Running a longer minimization (as suggested by @xy21hb)
   • Using a longer equilibration
   • Using more lambda windows

For anyone reading this in the future, this is hardly a PyAutoFEP bug, but rather a system-specific issue. Use the check list above to guide you in diagnosing.