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

[Justin Lemkul]

On 4/29/18 5:48 PM, Eric Smoll wrote:
> 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?

What you need to demonstrate is that the potential energy of the 
configuration using the MM energy is equivalent to that of the QM 
calculation. That requires the removal of all restraints/biases when 
evaluating the energy.

-Justin

> "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
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-- 
==================================================

Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

303 Engel Hall
340 West Campus Dr.
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jalemkul at vt.edu | (540) 231-3129
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