Refine selection of atoms in REST region using simple heuristic

[mcwitt]

The initial implementation of REST in single topology transformations in #1424 applies temperature scaling to all ligand-environment nonbonded interactions, and all ligand-ligand proper torsions that are rotatable or in aliphatic rings. I.e., the "REST region" (here, the set of ligand atoms whose interactions may potentially be scaled), is implicitly all of the combined ligand atoms.

This PR refines the REST region using a simple heuristic: a combined ligand atom in included iff it is involved in a bond, angle, or improper torsion interaction whose parameters differ between the end states of the transformation. The logic for scaling the relevant interactions is retained from the previous version, except that we now exclude interactions from scaling that do not involve an atom in the REST region.

This is intentionally a very minimal heuristic. Later on, we might extend this for example to include in the REST region ligand atoms that are not directly mutated in the transformation, but are nearby (e.g. by graph distance) to a mutation.

This PR also adds a utility to visualize the REST region using py3Dmol (similar to the existing view_atom_mapping_3d). Example from the hif2a public benchmark:

TODO:

• add tests exercising heuristic
• rebase once Speed-up setup_intermediate_state by 30x #1523 is merged

[mcwitt]

Closing temporarily. The REST region inference needs more thought; the current approach incorrectly includes all ligand atoms in the REST region if there is a mutation of any ligand atom due to the ligand-ligand pair interaction parameters changing.

[mcwitt]

Closing temporarily. The REST region inference needs more thought; the current approach incorrectly includes all ligand atoms in the REST region if there is a mutation of any ligand atom due to the ligand-ligand pair interaction parameters changing.

Addressed this by moving to a heuristic only considering differences in bond, angle, and improper torsion valence parameters (dummy atoms are always included in the REST region). This heuristic seems to produce reasonable-looking REST regions in a few examples, but needs further validation.

[proteneer]

awesome!