[gmx-users] Free Energy calculations crash for lambdas higher than 0.8

[Julian]

Dear Gromacs users,

I want to do free energy calculation for a receptor and the two ligands
immepip and methimepip.
Both ligands are almost the same except for a methylgroup instead of a
hydrogen.

I have created a dual topology file, and I convert one hydrogen + three
dummy atoms into a carbon + three hydrogen atoms.
Setting up dual topologies is always a bit tricky, but I am quite sure that
I haven't made any mistake here. However i attach the file.

The error I get for lambdas above 0.8 is:

Fatal error:
XX particles communicated to PME node 0 are more than 2/3 times the cut-off
out of the domain decomposition cell of their charge group in dimension x.
This usually means that your system is not well equilibrated.

However I think that the equilibration is good. I want to do the following
steps:

- Steepest Descent Minimisation
- Leap Frog Minimisation
- Double Precision Minimisation
- Simulated Annealing ( 300K -> 350K -> 300K )
- NVT md
- NPT md

Followed by the production run md.

But for higher lambdas I never get this far as it crashes as soon as I try
a md simulation (simulated annealing or nvt).

I am using very small time steps (dt = 0.0001), I have tried various
binding starting positions for the ligand, but it doesn't help.
I don't get high forces in the minimisations and in general the system
looks fine to me. Also I can run the simulation with the normal topology
without any problems.

Is my approach wrong? So far I am moving with all fep-lambdas from one
topology to the other. Do I have to fine-tune this part?

free_energy              = yes
init_lambda_state    = 100
fep_lambdas             = 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09
0.10 0.11 0.12 0.13 0.14 0.15 0.16 0.17 0.18 0.19 0.20 0.21 0.22 0.23 0.24
0.25 0.26 0.27 0.28 0.29 0.30 0.31 0.32 0.33 0.34 0.35 0.36 0.37 0.38 0.39
0.40 0.41 0.42 0.43 0.44 0.45 0.46 0.47 0.48 0.49 0.50 0.51 0.52 0.53 0.54
0.55 0.56 0.57 0.58 0.59 0.60 0.61 0.62 0.63 0.64 0.65 0.66 0.67 0.68 0.69
0.70 0.71 0.72 0.73 0.74 0.75 0.76 0.77 0.78 0.79 0.80 0.81 0.82 0.83 0.84
0.85 0.86 0.87 0.88 0.89 0.90 0.91 0.92 0.93 0.94 0.95 0.96 0.97 0.98 0.99
1.00
calc-lambda-neighbors    = -1

Thank you very much for your help!
Julian