Using RMSD in TorsionProfile fitting
- Joshua Horton
During torsion profile fitting we allow a slight MM relaxation of the molecule with 1kcal/mol restraints on all atoms not involved in the target dihedral. We recently looked into the effect of removing the restraints and for the small set of molecules saw a very similar performance in the resulting torsion profiles. However, we see much larger RMSD deviations during the fitting as the molecule fully relaxes. In this experiment, we have changed the torsion profile target to remove the restraints and use the RMSD deviations as part of the ForceBalance objective function. This should lead to both improved PES and lower RMSD between the MM and QM predicted structures.
Implementation
To do this we have looked at two possible similar methods that involve using the opt_geo target in combination with torsion profiles. This also gives us the ability to chose which internal degrees of freedom contribute to the objective function. In this example we only include dihedrals with a denom of 50, all other terms have a denom of 0.
Option 1, Set up a standard opt geo target for each grid point on the torsion drive with no restraints or frozen atoms. Fit these with each torsion profile.
Option2, Change the torsion profile target to compute the opt geo objective after each frozen optimization. This gives us a vector with the same length as the torsion profile where each value is the opt_geo dihedral only objective value, this is then added to the energy differences to give the total combined objective value.
return ((np.sqrt(self.wts)/self.energy_denom) * np.abs(compute.emm - self.eqm)) + ((np.sqrt(self.wts)/2 * total_ic_diff))Option 1
This option was run by Trevor and the forcebalance tables will be updated later here we only have the validation torsion drives.
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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No restraints | 
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| openff-1.0.0 RMSE 1.9340226158607 kcal/mol
gaff-2.11 RMSE 1.1407243538497651 kcal/mol
bespoke RMSE 0.3873825776904058 kcal/mol
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RMSD |
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| openff-1.0.0 RMSE 1.9340226158607 kcal/mol
gaff-2.11 RMSE 1.1407243538497651 kcal/mol
bespoke RMSE 1.0285332638632987 kcal/mol
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Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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No restraints | 
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RMSD |
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Option 2
State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
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initial (without restraints) | 90 | -45 | 0 - 4.027 | -0.123 - 2.616 | 0.606 | 0.9598 |
final (without restraints) | 90 | 90 | 0 - 4.027 | 0 - 3.907 | 0.277 | 0.2493 |
initial (with RMSD ) | 90 | -45 | 0 - 4.027 | -0.123 - 2.616 | 0.606 | 0.9598 |
final (with RMSD) | 90 | 90 | 0 - 4.027 | 0 - 3.915 | 0.274 | 0.1919 |
initial (restraints + RMSD) | 90 | 90 | 0 - 4.027 | 0-2.810 | 0.108 | 0.7937 |
final (restraints + RMSD) | 90 | 90 | 0 - 4.027 | 0-4.036 | 0.092 | 0.2251 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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No restraints |
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RMSD | 
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Restraints + RMSD | 
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State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
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initial (without restraints) | -105 | 135 | 0 - 1.355 | -1.058 - 0.640 | 0.206 | 1.2118 |
final (without restraints) | -105 | 60 | 0 - 1.355 | -0.132 - 1.192 | 0.170 | 0.1878 |
initial (with RMSD ) | -105 | 135 | 0 - 1.355 | -1.058 - 0.640 | 0.206 | 1.2118 |
final (with RMSD ) | -105 | 60 | 0 - 1.355 | -0.114 - 1.191 | 0.164 | 0.1711 |
initial (restraints + RMSD) | -105 | 120 | 0 - 1.355 | -1.020 - 0.732 | 0.087 | 1.1512 |
final (restraints + RMSD) | -105 | 60 | 0 - 1.355 | -0.142 - 1.229 | 0.084 | 0.190 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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No restraints |
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RMSD | 
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Restraints + RMSD | 
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No regularization
Here we run the RMSD fit again and the no restraint standard fitting without regularization to compare the difference.
State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (without restraints) | 90 | -45 | 0 - 4.027 | -0.123-2.616 | 0.606 | 0.9598 |
final (without restraints) | 90 | 90 | 0 - 4.027 | 0-4.014 | 0.328 | 0.0117 |
initial (with RMSD ) | 90 | -45 | 0 - 4.027 | -0.123-2.616 | 0.606 | 0.9598 |
final (with RMSD) | 90 | 90 | 0 - 4.027 | 0 - 4.551 | 0.288 | 0.1499 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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No restraints | 
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RMSD | 
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State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (without restraints) | -105 | 135 | 0 - 1.355 | -1.058-0.640 | 0.206 | 1.2118 |
final (without restraints) | -105 | -105 | 0 - 1.355 | 0-1.347 | 0.242 | 0.0237 |
initial (with RMSD ) | -105 | 135 | 0 - 1.355 | -1.058-0.640 | 0.206 | 1.2118 |
final (with RMSD ) | -105 | 60 | 0 - 1.355 | -0.112-1.124 | 0.159 | 0.1571 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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No restraints | 
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RMSD | 
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