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

[Nash, Anthony]

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
For more information and tips for troubleshooting, please check the GROMACS
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