Fit 0
Input FF:
Parameters to optimize:
['TIG0', 'TIG1a', 'TIG1b'] - General torsions
['TIG1c', 'TIG1d', 'TIG2', 'TIG3', 'TIG4', 'TIG5a', 'TIG5b', 'TIG6', 'TIG7', 'TIG8'] - interpolated
Targets:
'Fragment Stability Benchmark'
'OpenFF Gen 2 Torsion Set 1 Roche 2'
'OpenFF Gen 2 Torsion Set 2 Coverage 2'
'OpenFF Gen 2 Torsion Set 3 Pfizer Discrepancy 2'
'OpenFF Gen 2 Torsion Set 4 eMolecules Discrepancy 2'
'OpenFF Gen 2 Torsion Set 5 Bayer 2'
'OpenFF Gen 2 Torsion Set 6 Supplemental 2'
'OpenFF Group1 Torsions'
'OpenFF Group1 Torsions 2'
'OpenFF Group1 Torsions 3'
'OpenFF Rowley Biaryl v1.0'
'OpenFF Substituted Phenyl Set 1'
'OpenFF-benchmark-ligand-fragments-v1.0'
'SMIRNOFF Coverage Torsion Set 1'
Total number of targets excluding Lim Mobley benchmarks = 2746
QCA tdr_objects to exclude are in this file
Fit 1
Input FF:
Without excluding the in-ring torsions
Parameters to optimize:
['TIG0'] - General torsion
['TIG1c', 'TIG1d', 'TIG2', 'TIG3', 'TIG4', 'TIG5a', 'TIG5b', 'TIG6', 'TIG7', 'TIG8'] - interpolated
Targets: same as in Fit 0
Fit 2
Breaking up the interpolated parameters into single, aromatic and double (wherever possible) bond general torsion terms. Naming these as extensions of earlier TIG parameters appended by p, q, r for single, aromatic and double bonds repsectively. Wherever a carbonyl carbon is implied on the central bond there are no central double bonds, so not all parameters will have ‘r' extension. Excluding the high torsion barrier filters TIG1a, 1b so that double and aromatic bonds won’t get filtered.
Input FF:
Parameters to optimize:
['TIG0', ‘TIG1cp', ‘TIG1cq', ‘TIG1dp', ‘TIG1dq', ‘TIG1dr', ‘TIG2p', ‘TIG2q’, ‘TIG2r’, ‘TIG3p’, ‘TIG3q’, ‘TIG3r’, ‘TIG4p’, ‘TIG4q’, ‘TIG4r’, ‘TIG5ap’, ‘TIG5aq’, ‘TIG5bp’, ‘TIG5bq’, ‘TIG5br’, ‘TIG6p’, ‘TIG6q’, ‘TIG6r’, ‘TIG7p’, ‘TIG7q’, ‘TIG7r’, ‘TIG8p’, 'TIG8q’ ]
Targets: same as in Fit 0
Fit 3
Corrected the phase of non-interpolated parameters (from Fit 2)
Results of fits
Objective fn. | Full |
Fit 0: TIG* | 5.4766E+03 |
Fit 1: TIG* without filtering ring-torsions | 5.4807E+03 |
Fit 2: non-interpolated with 2 phases | 3.0181E+05 |
Fit 3: non-interpolated with 1 phase | 6.6621e+03 |
Chaya’s dataset only using fit0-FF | 3.2455E+02 |
OpenFF_1.3.0 (Iter 0 on TIG dataset) | 5.9620E+03 |
Iter 0 with CN, or CC central bonds only | |
CN only TIGs [1a, 1c, 1d, 2, 6, 7, 8] + [t43, 44, 45] | 5.4844E+03 |
CC only TIGs [0, 1b, 3, 4, 5a, 5b] + [t69, 69a, 76, 77, 78] | 5.8771E+03 |
Fit0 is better than 1.3.0 from the objective function values in the above table. Among CN and CC central bonds, CN has a lower objective function value and thus effect of CC is more dominant on the overall objective function.
Some of the better looking TD curves are:
SMILES | QM Vs MM | Structure |
|---|---|---|
COc1cccnc1-n1cccn1 |  |  |
CC(=O)Nc1cccs1 |  |  |
CN(C)c1ccccc1-c1ccccn1 |  |  |
Comparing MM Fits 0, 3 and 1.3.0 with QM
Fit 0 with all the TIG* parameters, and fit 3 is the non-interpolated version i.e., interpolated TIG params split into single, double and aromatic terms, compared with 1.3.0_unconstrained, and QM data.
File:
Assigned param in fit0-FF | QM-MM relative energies | Structure |
|---|---|---|
TIG1a |  |  |
TIG1a |  |  |
TIG3 |  |  |
TIG6 |  |  |
TIG1b |  |  |
t104 |  |  |
TIG1a |  |  |
TIG3 |  |  |
TIG1a |  |  |
TIG4 |  |  |
TIG1a |  |  |
TIG1b |  |  |
TIG1b |  |  |
TIG4 |  |  |
TIG3 |  |  |
TIG4 |  |  |
TIG3 |  |  |
TIG7 |  |  |
TIG3 |  |  |
TIG1a |  |  |
t58 |  |  |