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

qasimpars at gmail.com qasimpars at gmail.com
Mon Jan 2 15:19:56 CET 2017

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?
> -- 
> Gromacs Users mailing list
> * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before posting!
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or send a mail to gmx-users-request at gromacs.org.

More information about the gromacs.org_gmx-users mailing list