A tutorial on writing custom restraints using the PMI interface of the Integrative Modeling Platform software.

This was presented as a brief workshop at the MASFE 2023 conference.

The custom restraints used here are taken from the nblib library, written for modeling nanobody epitopes on target receptors (published here).

• restraints.py implments two custom restraints written using the RestraintBase PMI class. CenterPatchRestraint constrains the min. distance between a potential epitope center on a receptor with the paratope region of the binder molecule (in this case the nanobody). PatchPatchRestraint approximates shape complementarity between a proposed epitope on the target and the paratope on the nanobody. The epitope center on the receptor is essentially a escape mutation in the context of viral epitopes.

• modeling.py is a driver script that combines the above restraints with the usual ExcludedVolumeSphere and ConnectivityRestraint restraints in PMI to determine the binding mode of a given nanobody on the SARS-CoV-2 spike protein Receptor Binding Domain (RBD).

• data contains the topology, pdb and escape mutation data required for modeling.

• demo_<date>_.. folders contained short runs and ChimeraX sessions (called playback.cxs) from sampling using a single starting conformation.