[gmx-users] forward and backward states for the binding free energy energy

[qasimpars at gmail.com]

Thanks. I am looking forward to get Justin's respond as well.



> On 2 Jan 2017, at 15:40, Hannes Loeffler <Hannes.Loeffler at stfc.ac.uk> wrote:
> 
> On Mon, 2 Jan 2017 14:17:56 +0300
> Qasim Pars <qasimpars at gmail.com> wrote:
> 
>> 1-) The mean of the forward state is ~15 kcal/mol. That is too big,
>> right? Maybe the ligand doesn't get decoupled in the forward state?
> 
> It will be hard to guess whether this is meaningful or not...  You
> switch with 100 ps and carry out 50 replicates.  Is that maybe to fast
> or will you need more repetitions?  Experimentation (with monitoring of
> the results an convergence), comparison to equilibrium runs, and
> literature search should help.
> 
> There are many reasons why your current results may not match
> expectations. You don't quite say where the "literature" results come
> from.  You also don't say if you have closed the thermodynamical cycle
> properly or if you take any measurements regarding the vanishing end
> state.
> 
> 
>> 2-) Is the free energy control stuff used in the em.mdp, nvt.mdp,
>> npt.mdp and md.mdp correct for the forward and backward/reversible
>> state simulations? I must use the same free energy control parameters
>> in both states except init-lambda?
> 
> What you need to do is to prepare a number (equal to the number of
> trajectories you plan to run in the fast-switching runs) of equilibrated
> starting points for each end state. You have various ways to do that
> with Gromacs. If you want to use the same control parameters as in the
> free energy runs, as you plan to do it, you can use init-lambda=0.0 with
> a positive delta-lambda increment and init-lambda=1.0 with a negative
> increment.
> 
> 
>> 3-) Is the free energy control stuff used for 100 ps simulations of
>> the forward and backward/reversible state simulations correct? The
>> only difference between both states must be delta-lambda?
> 
> Plus init-lambda as in answer to 2.
> 
> 
>> 5-) I added the state B parameters to the
>> [ intermolecular_interactions ] parts. That should be enough to
>> define the state B of a molecule in GROMACS2016?
> 
> I think the state B topology will be created automatically with
> couple-moltype.  Why do you feel like modifying this by hand?
> -- 
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