Sulfonamide issue in Parsley
- Hyesu Jang
During the course of MD in a bound structure, NH2 of the sulfonamide is being pulled in close to the SO2 oxygens. The O-S-N angles go down to around 72 degrees and the distance between oxygen and hydrogen goes down to around 1.7 angstroms.
Test simulation with a simple sulfonamide in water showed the same pathology, while it did not happen when using SMIRNOFF99Frosst.
Parsley parameters
| SMIRNOFF99Frosst | Parsley 1.2 | Parsley 1.3 |
|---|---|---|---|
a30 | 109.5 / 140.0 | 104.2 / 201.1 | 99.1 / 220.7 |
a31 | 109.5 / 120.0 | 96.3 / 152.3 | 89.8 / 188.4 |
* equilibrium angle (degree) / force constant (kcal/mol)
The equilibrium angles of a30 and a31 decreased while their force constants increased. And during the refitting of Parsley 1.2, the values moved further away from the very initial points (in SMIRNOFF99Frosst).
Direction of the inspection
Origin of the counter-intuitive final equilibrium angles in Parsley 1.2
Possible need of higher-order terms in angle (or other bonded) potential energy function.
* Addition of a basic check of sulfonamide (or hypervalent nitrogen containing molecules) in ff release process. (like HMR canary test with propyne-containing molecules)