# [gmx-users] A charge group moved too... during backward transition of dual topologies

Nash, Anthony a.nash at ucl.ac.uk
Wed Aug 3 09:44:11 CEST 2016

Hi all,

I¹m performing free energy calculations based on Crooks Fluctuation
Theorem. To do this I¹ve used PMX to implement a dual topology. To keep
things simple, it is a transmembrane polyleucine helical protein where one
leucine is transforming into a serine - then there is the backward
transition of serine into Leucine, required for the overlap of two
gaussian distributions (forward and backward).

I have a very complicated arrangement of steps to equilibrate the system,
in very brief I have only included those involved once the protein is
embedded in the bilayer (bilayer eq was around 40 ns over various stages).
For a backward eq (serine->leucine) I used the parameters:

free_energy = yes
init_lambda = 1                 ;0=forward 1=backward
delta_lambda = 0                ;equilibrium
nstdhdl = 1
sc-coul = yes
sc-alpha - 0.3
sc-sigma = 0.25
sc-power = 1

And the eq steps:

-Steepest descent (<100 kjmol threshold)
-NVT 100ps (carbon-alpha posres 1000 kjmol)
-NPT 100ps (carbon-alpha posres 1000 kjmol - Berendsen pressure)
-NPT 10ns (carbon-alpha posres 1000 kjmol - PR pressure)
-NPT 2.5 ns (turn OFF posres)

The above steps produce a system with serine in the polyleu. I then
discard the first 1.5 ns and take 10 sets of coordinates and velocities
from the last 1ns. This is for my Œfast¹ backward (serine->leucine) 100 ps
transformation using the MDP parameters:

free_energy = yes
init_lambda = 1                 ;0=forward 1=backward
delta_lambda = -0.00002         ;transitions
nstdhdl = 1
sc-coul = yes
sc-alpha - 0.3
sc-sigma = 0.25
sc-power = 1

When I run the 10 Œfast¹ transition production runs approximately half of
them immediately result in the error:

Step 5:
The charge group starting at atom 63445 moved more than the distance
allowed by the domain decomposition (1.420000) in direction Z
distance out of cell 70.681579
Old coordinates:  -48.465  256.312   81.655
New coordinates:  -48.465  256.312   81.655
Old cell boundaries in direction Z:    5.728   10.974
New cell boundaries in direction Z:    5.728   10.974

-------------------------------------------------------
Program mdrun_mpi_d, VERSION 5.0
Source code file:
/home/sacat2/gromacs_source/gromacs-5.0/src/gromacs/mdlib/domdec.c, line:
4380

Fatal error:
A charge group moved too far between two domain decomposition steps
This usually means that your system is not well equilibrated
website at http://www.gromacs.org/Documentation/Errors
-------------------------------------------------------

I understand what this error means, but I was wondering whether I was
doing something far more fundamentally wrong, given that every forward
transition (same eq set up, just using init_lambda = 0 and delta_lambda =
0.00002) never produce this error! They always work, and monitoring my
work gives me an amazing gaussian distribution.

I have put the 2.5ns production run with no position restraints up for a
further 2.5 ns, and I¹m testing whether frames from the last ns produce
similar errors i.e., does the inclusion of serine require further
equilibration.

I would appreciate any thoughts.

Many thanks
Anthony