Sage 2.1.0 Release Candidate 1

The new force field files in this release are adapted from fb-fit/result/optimize/force-field.offxml in release_2.1.0-rc.1.tar.gz from the Assets of this release. This tarball is a modified state of https://github.com/openforcefield/sage-2.1.0 at the time this was fit.

This force field is applicable to druglike molecules consisting of the elements C, H, O, N, P, S, F, Cl, Br, and I, and the monoatomic ions Li+, Na+, K+, Rb+, F-, Cl-, Br-, and I-. The parameters have been co-optimized to TIP3P water, therefore this force field also contains parameters for TIP3P, including bond length constraints.

Version 2023.02.1 Initial Water Model Ports

This release adds our initial attempt at porting TIP3P and TIP3P-FB water models with Juong-Cheatham ion parameters. See docs/water-models.md for more information, and thescripts/ directory for the code to regenerate the force field files.

Version 2.0.0 "Sage"

This force field is identical to 2.0.0-rc.2 Sage except that:

• The parameter IDs have been renumbered to be sequential in all sections (for example, t70d is now t79). For more information see openforcefield/openff-sage#1 and the attached old-id-to-new-id-map.json file.
• The openff_unconstrained-2.0.0.offxml file has had TIP3P geometry constraints added, but all other hydrogen bonds remain unconstrained.
• Formatting cleanup and cosmetic changes

This force field is applicable to druglike molecules consisting of the elements C, H, O, N, P, S, F, Cl, Br, and I, and the monoatomic ions Li+, Na+, K+, Rb+, F-, Cl-, Br-, and I-. The nonbonded parameters in this force field were optimized assuming use with TIP3P water, and so TIP3P parameters are included in the force field.

Version 2.0.0-rc.2 "Sage" Release Candidate

This major release candidate is identical to v2.0.0-rc.1 Sage except that the angle value for a16 has been changed to 180.0 * degree, as the previous value of 183 * degree causes geometry optimizers to fail to converge.

This force field is applicable to druglike molecules consisting of the elements C, H, O, N, P, S, F, Cl, Br, and I, and the monoatomic ions Li+, Na+, K+, Rb+, F-, Cl-, Br-, and I-. The nonbonded parameters in this force field were optimized assuming use with TIP3P water, and so TIP3P parameters are included in the force field.

Provided that early use of this force field shows no major deficiencies, this may be promoted to the full Sage release.

Version 2.0.0-rc.1 "Sage" Release Candidate

The contents of this major release candidate are adapted from https://github.com/openforcefield/openff-sage/releases/tag/2.0.0-rc.1. See that release's notes and assets for more details.

Provided that early use of this force field shows no major deficiencies, this may be promoted to the full Sage release.

Version 1.3.1 "Parsley" Update

This bugfix release is identical to 1.3.1-alpha.1. Please see those release notes (https://github.com/openforcefield/openff-forcefields/releases/tag/1.3.1-alpha.1) for details.

Version 1.3.1-alpha.1 "Parsley" Update candidate

Short summary

The new force field files in this release are adapted from the openff-1.3.0 release, except that two angle parameters have been reverted to their original values from smirnoff99Frosst 1.1.0.

Full Summary

The ability of the Parsley line of force fields ability to reproduce the tetrahedral geometry of certain sulphonamides (especially primary sulphonamides) has progressively and subtly degraded between releases, cumulating in OpenFF 1.3.0 yielding a O-S-N valence angle of < 90 deg for certain molecules while angle of ~109.5 would be more expected.

Simulating CC1=CC=C(C=C1)S(=O)(=O)N in vacuum using OpenFF 1.3.0, for example, shows an average O-S-N valence angle of 76.26 (+/- 0.21)

This issue has been tracked to the a30 ([*:1]~[#16X4:2]~[*:3]) and a31 ([*:1]-[#16X4,#16X3+0:2]-[*:3]) valence angle parameters, whereby the equilibrium angle has monotonically reduced while simultaneously the force constant has increased:

 ---------------------------------------------------------- 
|     | SMIRNOFF99Frosst |  Parsley 1.2.0 |  Parsley 1.3.0 |
|     |------------------|----------------|----------------|
|     | k     | theta    | k     | theta  | k     | theta  |
|-----|-------|----------|-------|--------|----------------|
| a30 | 140.0 | 109.5    | 201.1 | 104.2  | 220.7 |  99.1  |
| a31 | 120.0 | 109.5    | 152.3 |  96.3  | 188.4 |  89.8  |
 ---------------------------------------------------------- 
(k in kcal / mol, theta in deg)

This has seemingly in turn resulted in the degradation of protein-ligand binding free energies for certain molecules which contain sulphonamide moieties (primarily primary sulphonamide groups). This potentially also affects related hypervalent substituents (e.g. hypervalent nitrogens) although currently only issues with sulphonamides has been observed.

We believe this issue arose due to the valence angle being trained to both sulphur containing rings in addition to molecules where the sulphur would be expected to be tetrahedral, whereby ring containing sulphur molecules would likely drive the angles to be smaller than 109.5 degrees. We are now actively working to validate this hypothesis and come up with a sustainable resolution for future releases.

For now given the potential severity of the issue, it has been decided that we will make an alpha patch release of OpenFF 1.3.0, numbered OpenFF 1.3.1-alpha.1, which has the values of a30 and a31 reset to their smirnoff99Frosst 1.1.0 values.

Provided that benchmarks show this issue as resolved OpenFF 1.3.1-alpha.1 will become a full release -> OpenFF 1.3.1.

Version 1.3.0 "Parsley" Update

The new force field files in this release are adapted from result.offxml in release_1.3.0.tar.gz from the Assets of Version 1.3.0 "Parsley". See that release page for more details.

Version 1.2.1 "Parsley" Update

This bugfix release manually changes two bond force constants (b24 and b27) to resolve an issue seen in propyne substituents when using hydrogen mass repartitioning with a 4fs timestep. Full details are available at #19 and in the reproduce_propyne_hmr.ipynb notebook in the release assets on GitHub.

Version 1.2.0 "Parsley" Update

The new force field files in this release are adapted from result.offxml in release_1.2.0.tar.gz from the Assets of Version 1.2.0 "Parsley" Update. See that release page for more details.