[gmx-users] Perturbation Thermodynamic Integration

[Dan Gil]

>
> What does grompp from 2016.3 report?
>

ERROR 1 [file topol.top, line 10]:
  Atom 1 in molecule type 'HEPT' has different A and B state charges and/or
  atom types set in the topology file as well as through the mdp option
  'couple-moltype'. You can not use both these methods simultaneously.

If you do this via decoupling ("absolute" transformation) you do that
> once for molecule A and once for molecule B.


I believe you are referring to the BAR method? I am trying to see if I get
the same results as another group. They used thermodynamic integration from
A to B, so I decided to spend some more time with this. I will try later if
I get consistent results for both methods.

If you want to do this via a relative transformation you would not use
> couple-moltype at all but fill in the B columns in your topology file
> for all force field parameters that change.


I've filled in the B columns, but I didn't realize that I should not use
couple-moltype. I will remove the following lines from mdp file.

couple-moltype           = HEPT
> couple-lambda0           = vdwq
> couple-lambda1           = none
> couple-intramol          = no


Then, grompp reports no errors.

transforming the masses may interact badly
> with bond constraints that are applied to alchemically transformed
> bonds


Thank you for this information! Do you know if there are there publications
that refer to this issue?

On Tue, May 16, 2017 at 10:46 AM, Hannes Loeffler <
Hannes.Loeffler at stfc.ac.uk> wrote:

> On Tue, 16 May 2017 10:28:08 -0400
> Dan Gil <dan.gil9973 at gmail.com> wrote:
>
> > Thank you for the advice on the cut-off schemes and PME methods.
> >
> > What is the physical meaning of a non-interacting final state
> > > that has different masses from the initial state?
> >
> >
> > These free energy options was just from me trying to figure out why
> > mass has any contributions at all. I am going from molecule A to B
> > described in the topology. In the actual simulations, I am planning
> > on using this: vdw_lambdas              = 0 0.1 0.2 0.3 0.4 0.5 0.6
> > 0.7 0.8 0.9 1 coul_lambdas             = 0 0.1 0.2 0.3 0.4 0.5 0.6
> > 0.7 0.8 0.9 1 bonded_lambdas           = 0 0.1 0.2 0.3 0.4 0.5 0.6
> > 0.7 0.8 0.9 1 restraint_lambdas        = 0 0.1 0.2 0.3 0.4 0.5 0.6
> > 0.7 0.8 0.9 1 mass_lambdas             = 0 0.1 0.2 0.3 0.4 0.5 0.6
> > 0.7 0.8 0.9 1
> >
> > To get the solvation free energy difference between molecule A and B.
>
> If you do this via decoupling ("absolute" transformation) you do that
> once for molecule A and once for molecule B.  I don't see why you would
> want to change masses in this case.
>
> If you want to do this via a relative transformation you would not use
> couple-moltype at all but fill in the B columns in your topology file
> for all force field parameters that change.  In this case you _can_
> change the masses but you would have to do the same transformation in
> vacuum. Then the mass contributions should cancel perfectly (at least in
> the limit of infinite sampling, I guess).  But Michael Shirts has
> commented a while back that transforming the masses may interact badly
> with bond constraints that are applied to alchemically transformed
> bonds (we have seen problems with this too). So it is just simplest to
> not use mass-lambdas precisely because of the aforementioned argument.
>
>
> Cheers,
> Hannes.
> --
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