[gmx-users] Dummy atoms flopping everywhere

[Alessandra Villa]

Hi

On Wed, Nov 27, 2019 at 1:44 PM Raphaël Robidas <raphaelrobidas at gmail.com>
wrote:

> Hello,
>
> Thank you for your suggestion! I tried it and the benzyl isn't flopping
> around uncontrollably, and I get much more reasonable FEP energies.
>
> I am still wondering one thing: I used LigParGen to generate the hybrid
> topology of my two ligands. I can see that it is morphing the atoms in the
> benzyloxy group  to dummy atoms with mass 1.0080 (even carbon atoms):
>
> [ atoms ]
> ;   nr       type  resnr    res   atom   cgnr     charge       mass
>  typeB    chargeB      massB comments
>      1   opls_800      1    A2B    H00      1     0.1293     1.0080
>  opls_9855     0.0000     1.0080
>      2   opls_801      1    A2B    C01      1    -0.1350    12.0110
>  opls_9856     0.0000     1.0080
>      3   opls_802      1    A2B    C02      1    -0.1431    12.0110
>  opls_9857     0.0000     1.0080
>
> ...
>
>
> Is this another technique of dealing with dummy atoms? All the relative
> free energy perturbation tutorials I have seen use very small perturbations
> (ex. substituants on aryls), so I am not sure exactly how to deal with this
> larger change. Any help/pointers are greatly appreciated!
>
>
In case  you are not interested in the contribution from the kinetic energy
to free energy,
better to keep the mass constant between state A and B.

see
http://manual.gromacs.org/current/reference-manual/algorithms/free-energy-calculations.html

Best regards
Alessandra


> Best
>
> Le mer. 27 nov. 2019 à 03:26, Alessandra Villa <
> alessandra.villa.biosim at gmail.com> a écrit :
>
> > Hi,
> >
> > On Mon, Nov 25, 2019 at 6:20 PM Raphaël Robidas <
> raphaelrobidas at gmail.com>
> > wrote:
> >
> > > I am doing a free energy perturbation calculation on a protein-ligand
> > > system. I am going from a topology A which has a benzyloxy group to a
> > > topology B which only has a methoxy group. My problem is that when
> > lambda =
> > > 1, the simulation crashes because the benzyloxy group is flopping
> around
> > > too fast, since it has no mass nor collision. I am wondering that the
> > best
> > > way to deal with this would be.
> > >
> > >
> > If  you switch off only the non-bonded interactions when going from A to
> B,
> > this should not happen since  the bond interactions (e.i. torsion) are
> > still active for the benzyloxy group (thus the benzyloxy group can not
> > freely rotate).
> > Best regards
> > Alessandra
> >
> >
> > > Using restraints would be an option, but I don't need to restrain my
> > ligand
> > > otherwise, so it would be desirable to avoid restraints overall. Could
> a
> > > second topology without the dummy atoms be used just when lambda = 1 or
> > it
> > > won't be compatible with the rest of the simulations?
> > >
> > > Thank you!
> > > --
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