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

[Hannes Loeffler]

On Tue, 4 Oct 2016 14:01:52 +0300
Vlad <vlad_balaev at mail.ru> wrote:
> No reason. I just thought it would give the same result.  

In theory both directions should be symmetrical and give the same
result.


> In the trajectory the ligand diffuse to the end of the cell like a
> ghost through the water molecules. And could the reason lie in the
> fact that in the initial structure during all preparations the ligand
> is "fully existing" and in the first step of simulation suddenly is
> turned off?  


I would suggest to have a look through
http://www.alchemistry.org/wiki/Example:_Absolute_Binding_Affinity and
other material on that web page.  In particular reference 1 on that
page should be of interest to you in how to use restraints within a
general scheme.

In a homogeneous environment like water it doesn't matter that your
"ghost" molecule drifts because on average the interactions with its
environment will be the same regardless of location.  In an
inhomogeneous environment, however, the nearly non-interacting ligand
will have different probabilities of where it is located.  In
principle, you would have to sample _all_ possible locations which in
practice is hard or impossible.  Hence the restraint scheme as
suggested above.

Your ligand should exists as a bonded network throughout the
simulation.  What you are doing however is "decoupling" which means
that the non-bonded interactions between the ligand and its environment
and vice versa a gradually switched off.


Cheers,
Hannes.