TorsionProfile Restraints
It has been suggested that the use of restraints on the atoms not involved in the target torsion during Forcebalance optimization might affect the performance of the forcefield in recreating the QM PES outside of the fitting. To investigate this we have fit a collection of molecules from the BACE JACS benchmark system with and without the use of restraints. This is achieved by using the keyword restrain_k=0 on the torsion profile target. After the molecules have been refit a new torsiondrive was run using the same input conformers as used for the reference QM torsiondrive but with the new bespoke forcefield. The fitting was done using openff-bespokefit starting from openff-1.3.0.
The Forcebalance fits
Molecules with multiple rotatable bonds were fit simultaneously. Note that while the torsionprofile target in forcebalance calculates and reports the RMSD it is not used in the objective function to influence the parameters. Future investigations would need to implement this to see if it can help improve the performance of the fitting.
Here we show the results of the forcebalance fits comparing the RMSD with and without restraints.
BACE Molecule 0
Parent molecule
Fragments
State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (with restraints) | 135 | 30 | 0 - 2.247 | -0.031 - 2.360 | 0.022 | 0.0997 |
final (with restraints) | 135 | 30 | 0 - 2.247 | -0.196 - 2.854 | 0.022 | 0.3428 |
initial (without restraints) | 135 | -150 | 0 - 2.247 | -0.197 - 2.854 | 0.022 | 0.3430 |
final (without restraints) | 135 | 30 | 0 - 2.247 | -0.032 - 2.360 | 0.022 | 0.0997 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
|---|---|---|---|---|
Restraints |  |
|
| openff-1.0.0 RMSE 0.09704657370122952 kcal/mol
gaff-2.11 RMSE 0.15280628178403974 kcal/mol
bespoke RMSE 0.09295927754739428 kcal/mol
|
No restraints |  |
|
| openff-1.0.0 RMSE 0.09704657370122952 kcal/mol
gaff-2.11 RMSE 0.15280628178403974 kcal/mol
bespoke RMSE 0.09328984947607974 kcal/mol |
State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (with restraints) | 0 | 150 | 0 - 3.196 | -0.959 - 4.368 | 0.084 | 1.0429 |
final (with restraints) | 0 | 165 | 0 - 3.196 | -0.288 - 3.286 | 0.095 | 0.1933 |
initial (without restraints) | 0 | 150 | 0 - 3.196 | -0.858 - 4.539 | 0.372 | 1.1034 |
final (without restraints) | 0 | 165 | 0 - 3.196 | -0.239 - 3.303 | 0.388 | 0.1823 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
|---|---|---|---|---|
Restraints | 
|
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| openff-1.0.0 RMSE 1.4843402452961 kcal/mol
gaff-2.11 RMSE 3.2504935679330975 kcal/mol
bespoke RMSE 0.21568580531766277 kcal/mol
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No restraints | 
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State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (with restraints) | -60 | -60 | 0 -7.208 | 0 - 10.991 | 0.106 | 1.5221 |
final (with restraints) | -60 | -60 | 0 -7.208 | 0 - 7.579 | 0.082 | 0.1848 |
initial (without restraints) | -60 | -60 | 0 -7.208 | 0 - 11.052 | 0.667 | 1.4610 |
final (without restraints) | -60 | -60 | 0 -7.208 | 0 - 7.763 | 0.412 | 0.1925 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
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Restraints | 
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No restraints | 
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BACE Molecule 1
Parent molecule
This molecule shares the biphenyl fragment with bace0 so those results are skipped
Fragments
State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (with restraints) | -105 | 120 | 0 - 1.355 | -1.020 - 0.732 | 0.087 | 1.1512 |
final (with restraints) | -105 | 60 | 0 - 1.355 | -0.138 - 1.218 | 0.085 | 0.1954 |
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 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
|---|---|---|---|---|
Restraints | 
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No restraints | 
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State | Min(QM) | Min(MM) | Range(QM) | Range(MM) | Max-RMSD angstrom | Energy-RMSE kcal/mol |
|---|---|---|---|---|---|---|
initial (with restraints) | 90 | 90 | 0 - 4.027 | 0 - 2.810 | 0.108 | 0.7937 |
final (with restraints) | 90 | 90 | 0 - 4.027 | 0 - 4.016 | 0.092 | 0.2479 |
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 |
Restraints | Forcebalance result | Torsiondrive PES | Torsiondrive RMSD | RMSE |
|---|---|---|---|---|
Restraints | 
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No restraints | 
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Overlap of the bespoke and QM structures at the torsion angle with the largest RMSD -90. This seems to be caused by the ring optimising to the mm minimum around 100