[gmx-users] free energy calculation

[Maik Goette]

You are probably starting your runs from a non equilibrated structure.
Assume, the system changes via a slow growth run.
The atoms may rearrange due to changes in their potentials.
Therefore it may be problematic, if you start from the same structure 
for different lambdas. Try simulating a one way slow growth and pick the 
snapshots close to your lambda value from the trajectory and start your 
"quasi-FEP" with those.

I can't answer your second question properly, because I don't know the 
code itself. But my guess is, that GROMACS calculates the potential for 
state A and B and then interpolates between them in a linear fashion 
(dependent of if you use soft-core or not). From this arises a yes for 
the second part of your question. If I'm wrong with that, I'm sure, 
someone who knows better will correct me quite fast. ;)

Regards

Maik Goette, Dipl. Biol.
Max Planck Institute for Biophysical Chemistry
Theoretical & computational biophysics department
Am Fassberg 11
37077 Goettingen
Germany
Tel.  : ++49 551 201 2310
Fax   : ++49 551 201 2302
Email : mgoette[at]mpi-bpc.mpg.de
         mgoette2[at]gwdg.de
WWW   : http://www.mpibpc.gwdg.de/groups/grubmueller/


Paolo Cerri wrote:
> Dear all,
> 
> I'm trying to calculate free energy differences using the standard
> method of thermodynamic integration.I calculate dG/dlambda for different
> values of lambda and then integrate.
> 
> When decoupling LJ interactions i have LINCS WARNING:
> 
> Step 1, time 0.002 (ps)  LINCS WARNING
> relative constraint deviation after LINCS:
> max 0.007366 (between atoms 7 and 8) rms 0.002535
> bonds that rotated more than 30 degrees:
>  atom 1 atom 2  angle  previous, current, constraint length
>       7      8   50.1    0.1010   0.1017      0.1010
>       9     10   65.8    0.1090   0.1085      0.1090
>      17     18   32.1    0.1010   0.1011      0.1010
>      17     19   32.0    0.1010   0.1011      0.1010
> [...]
> and eventually the simulation stops (during the equlibration run at
> lambda >= 0.9)
> 
> I obtain the following message:
> 
> -------------------------------------------------
> Program mdrun, VERSION 3.3.1
> Source code file: clincs.c, line: 559
>                                                                                                                                           
> Fatal error:
> Too many LINCS warnings (10001) - aborting to avoid logfile runaway.
> This normally happens when your system is not sufficiently
> equilibrated,or if you are changing lambda too fast in free energy
> simulations.If you know what you are doing you can adjust the lincs
> warning threshold
> in your mdp file, but normally it is better to fix the problem.
> --------------------------------------------------
> 
> I remark that in my simulations lambda is not changed continuously
> during simulation, but i perform several simulations at different fixed
> lambda values.
> 
> I change only LJ interactions (having previusly turned of Coulomb
> interactions)
> I use  Amber forcefield  ffamber99
> 
> thanks in advance
> 
> Paolo
> 
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