[gmx-users] Dihedral parameters from QM and MM relaxed surface scans

[Eric Smoll]

Mark,

*Thank you for the reply! *

I understand your conclusion but I am trying to rule out workflow errors on
my part before I make decisions based on the suitability of this
forcefield. Let's say I am testing a QM-geometry optimized molecule with
two identical (same parameters) and coupled dihedrals: phiA and phiB.

Across a QM dihedral relaxed surface scan (RSS), phiA is held at the
initial QM geometry optimized value and phiB is incremented across the 360
degrees of its rotation.
Thus, each step of the QM RSS has two dihedral restraints.

Then, each step of the associated MM RSS should use the same two dihedral
restraints relaxing all other DOF's. The results can be used to calculate a
"restrained" MM PES for phiB.

In this example, how should the "unrestrained" PES be computed with "mdrun
-rerun"? Should both dihedral restraints be removed across each step of the
MM PES scan? Or should the dihedral restrain on phiA stay?

"If the normal FF was parameterized for the species and configurations of
interest, then you'd observe that the unrestrained PES matched the
restrained PES, ie that the contributions from the restraint were
negligible."

I see. I did not make that connection. Thank you.

Best,
Eric

On Sun, Apr 29, 2018 at 3:13 PM, Mark Abraham <mark.j.abraham at gmail.com>
wrote:

> Hi,
>
> Your two PES scans are over the same coordinates, and by construction you
> are balancing the normal FF contributions against an intended-as-strong
> restraint. The only thing that is different between your two sets of PE
> calculation is the contribution of the restraint. If the normal FF was
> parameterized for the species and configurations of interest, then you'd
> observe that the unrestrained PES matched the restrained PES, ie that the
> contributions from the restraint were negligible. Clearly that isn't the
> case, so the only available conclusion is that the normal FF isn't suitable
> for modelling this PES. Whether that is a useful conclusion about the
> chances for quality observations of quantities that depend on the FES is
> less clear.
>
> Mark
>
> On Sat, Apr 28, 2018 at 9:30 AM Eric Smoll <ericsmoll at gmail.com> wrote:
>
> > Hello Gromacs Users,
> >
> > I am trying to reproduce some published forcefield development work. In
> > this paper, dihedral parameters are derived from QM and MM relaxed
> surface
> > scan data collected on individual small molecules in vacuum.
> >
> > My replication workflow is as follows. The MM relaxed surface scan
> > trajectory was prepared by concatenating the final frame of a set of
> energy
> > minimization calculations. Each energy minimization held the dihedral of
> > interest at a desired angle with a 1000 kJ/mol dihedral restraint. Other
> > DOF's were allowed to relax with the "steep" algorithm in
> single-precision
> > GROMACS 2018.1 to machine precision. A "restrained" dihedral PES was
> > calculated by collecting the molecule's potential as a function of
> dihedral
> > angle *with the restraint on the dihedral of interest*.
> >
> > An "unrestrained" dihedral PES was also calculated by removing the
> dihedral
> > restraint on the dihedral of interest and calculating the energy with the
> > rerun feature of mdrun.
> >
> > I find that the "restrained" MM dihedral PES is in excellent quantitative
> > agreement with QM relaxed surface scan data. The "unrestrained" MM
> dihedral
> > PES is only in qualitative agreement with the QM results. Peaks and dips
> in
> > the "unrestrained" PES are exaggerated when compared to the "restrained"
> > PES.
> >
> > As far as I understand, the "unrestrained" PES should be more
> > appropriate/accurate than the "restrained" PES. Am I correct? Is there a
> > flaw in my workflow?
> >
> > Best,
> > Eric
> > --
> > 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.
> >
> --
> 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.
>