[gmx-users] Clarity on TI free energy terms

[Hannes Loeffler]

On Wed, 1 Jun 2016 07:54:56 +0000
"Nash, Anthony" <a.nash at ucl.ac.uk> wrote:

> In the tutorial, charges are off in the topology and the electrostatic
> coupling to lambda remains 0 throughout the 20 windows. I assume
> setting col_lambdas=0 0 0 Š was for that very reason I.e., the
> charges were off? Could the charges not have been left on and
> col_lambdas defined similar to vdw_lambdas? 
> (I understand that if charges remain constant, as vdw turns off, the
> system will probably blow up as attraction brings molecules infinitely
> close).

Technically, Gromacs allows you to vary both vdW and Coulomb lambdas
simultaneously because Gromacs can apply softcore potentials to both.
In practice though it seems that many workers still prefer to separate
the two terms from each other.

 
> If my transition is from a small molecule into a small molecule e.g.,
> G-D-G to G-K-D, (the PMX paper) should I define all three lambdas:
> vdw_lambdas, col_lambdas and bonds_lambdas? Between states A and B,
> VdW, charges and bonds are all changing.

Lambda paths are only about separating the various force field terms
from each other.  If you do not explicitly state any of those lambda
vectors they will adopt they same lambdas as specified in fep-lambdas,
see manual.  I do not see a reason why you would want to separate out
the bonded terms as well.  They are subject to a linear transformation
only anyway.

What you may want to do is to keep the mass-lambdas at one end-point as
they can interact badly with constraints.  In a proper thermodynamic
cycle mass contributions must perfectly cancel.


Cheers,
Hannes.