[gmx-users] Separate lambdas for repulsive and dispersive free energies?

[Nuo Wang]

Hi Michael,

Thanks for your confirmation!

My goal is to use the "accurate" FEP hydration free energy components to
individually assess my continuum model calculated E_vdw_repulsive,
E_vdw_dispersive and E_elec (for our new continuum model package VISM, doi:
10.1002/jcc.23890).

E_vdw_dispersive and E_elec are easy to calculate in theory, but I don't
know how I can efficiently calculate E_vdw_repulsive for a protein using
the current FEP protocols. I am still looking for a method that calculates
E_vdw_repulsive for proteins on a higher resolution than continuum model,
any information on this will be of great help to me!

Thanks!
Nuo

On Sun, Mar 27, 2016 at 8:39 PM, Michael Shirts <mrshirts at gmail.com> wrote:

> Correct, currently a WCA decomposition has not been implemented.
>
> I'm not sure if I understand this comment, though:
>
> >  For this reason, I only plan to calculate E_vdw_dispersive and E_elec
> for my system.
>
> E_vdw_repulsive is a gigantic contribution to the solvation free
> energy of the protein. Why would you not calculate it?  Without it,
> you're calculating something else entirely.
>
> On Sun, Mar 27, 2016 at 8:44 PM, Nuo Wang <wolich22 at gmail.com> wrote:
> > Hi all,
> >
> > I am trying to calculate the hydration/solvation free energy for proteins
> > using free energy perturbation:
> > E_hydration = E_vdw + E_elec
> > E_vdw (WCA decomposition) = E_vdw_repulsive + E_vdw_dispersive
> >
> > However, unlike small molecules, if I turn off both elec and vdw for a
> > normal-sized protein, a huge cavity will be created and it will take
> > unfeasible amount of time to equilibrate the system. For this reason, I
> > only plan to calculate E_vdw_dispersive and E_elec for my system.
> >
> > I have read the mailing list posts of implementing the repulsive WCA
> > potential in Gromacs, but I have not found any discussion that try to
> > implement the WCA-decomposed potential, i.e. repulsive + dispersive, and
> > further scaling them separately in free energy calculations.
> >
> > According the the manual, it seems that it is impossible to implement the
> > decomposition with the Gromacs function form g(x) + f(x). On top of this,
> > vdw is scaled together by one lambda. I wonder if I am right on this and
> if
> > there is an alternative way that I am not aware of?
> >
> > FYI, the WCA decomposed scaling protocol has been implemented in CHARMM:
> > http://pubs.acs.org/doi/abs/10.1021/jp048502c
> >
> > Thanks,
> > Nuo
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