[gmx-users] Free energy calculation problem with too high dG

[Hannes Loeffler]

On Tue, 4 Oct 2016 15:27:25 +0300
Vlad <vlad_balaev at mail.ru> wrote:

> I tried to do the decoupling and strangely the result is not the same
> Below is the end of the log
> The total dG is significantly less then previous and the last dG
> value is particularly small I think total dG will get less with more
> precise lambda sampling (by 0.05 instead of 0.1) The thing which
> still is strange is the value of entropy for the last lambda (in the
> previous case it was so high as well for the first lambda)
> 
> So you suggest to use restraints
> Througout the simulation or also gradually switched off?

I suggest that you have a careful look at that web page and related
literature to understand how this type of simulation is supposed to
work. As per my previous explanation I do not see anything particularly
strange at this point.  Making a molecule disappear is just so much
simpler than making it appear.  In the latter case you may get away
with (much) longer equilibration (did you actually do prior
minimisation?).  You may also disrupt your system quite severely esp. in
the case of a protein environment.  Maybe a proper choice of positional
restraints may help.  But I am nor sure if going this route is really
worthwhile except for better understanding the method.  You will
however not get around a careful analysis of your simulations.


Cheers,
Hannes.