[gmx-users] Sampling a weak ligand

[Raphaël Robidas]

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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