[gmx-users] Sampling a weak ligand

[Александр Лашков]

What method do you use to calculate free energy? For MBAR if overlap matrix
around 0 lambda state is ok - that's ok.
Alexander

вт, 24 дек. 2019 г., 18:00 Raphaël Robidas <raphaelrobidas at gmail.com>:

> Hello,
>
> Here is part of my MDP:
>
> bonded_lambdas = 0.00 0.03 0.10 0.20 0.40 0.75 1.00 1.00 1.00 1.00 1.00
> 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00
> 1.00 1.00 1.00 1.00 1.00 1.00
> coul_lambdas =      0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.10 0.20 0.30
> 0.40 0.45 0.50 0.55 0.60 0.65 0.70 0.80 0.90 0.95 1.00 1.00 1.00 1.00 1.00
> 1.00 1.00 1.00 1.00 1.00 1.00
> vdw_lambdas =      0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
> 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.15 0.30 0.40 0.55
> 0.70 0.76 0.83 0.90 0.95 1.00
>
>
> As you can see, I am adding an intermolecular interaction. The problem is
> that at the state (0, 0, 0), the ligand can dissociate. I need that state
> to find the free energy of the interaction in solution.
>
> Are you saying that I actually don't need those states?
>
> Thanks for your replies,
>
> Best.
>
> Le mar. 24 déc. 2019 à 01:01, Александр Лашков <alashkov83 at gmail.com> a
> écrit :
>
> > Also, you may use the pull code in gromacs,
> > Alexander
> >
> > вт, 24 дек. 2019 г. в 07:47, Александр Лашков <alashkov83 at gmail.com>:
> >
> > > May be you should add intermolecular interaction as is in FEP
> calculation
> > > for protein-ligand complex.
> > > Alexander Lashkov
> > >
> > > вт, 24 дек. 2019 г., 3:05 Raphaël Robidas <raphaelrobidas at gmail.com>:
> > >
> > >> Hello all,
> > >>
> > >> I am running free energy perturbation calculations to determine the
> > >> absolute affinity of a weak ligand. To prevent dissociation and
> increase
> > >> sampling, the first few lambda states introduce a harmonic restraint
> via
> > >> the intermolecular interactions feature. The problem is that my ligand
> > >> dissociates in the first state, which has no restraint at all. Is
> there
> > a
> > >> technique to still get an accurate value? I plan on running a longer
> > >> simulation for the first state in order to sample more the bound
> state,
> > >> but
> > >> I hope that there is a smarter way!
> > >>
> > >> Thanks and happy holidays!
> > >> --
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