Transferability of the optimal locality threshold

Determine whether the optimal locality threshold for the sparse Potts interaction graph is specific to each protein system or transferable across different proteins.

Background

PHASE restricts pairwise Potts couplings to residue pairs whose Cα atoms approach within a prescribed spatial cutoff. In the A2A receptor analyses, a 6 Å cutoff provides a strong compromise between model locality and statistical fidelity, while a denser 10 Å graph yields limited additional improvement. The supplementary analysis confirms this behavior in the active, mini-Gs-coupled FApoG ensemble, suggesting that the selected cutoff is robust across distinct A2A conformational states.

The unresolved issue is whether this optimal locality threshold reflects a property of the A2A receptor and its data, or whether comparable cutoff values can be transferred to other proteins. Resolving this question would clarify how much system-specific validation is required when applying PHASE beyond the receptor studied in the paper.

References

This supports the use of a common 6~\AA{} cutoff across distinct conformational states of 2A, while leaving open whether the optimal locality threshold is system-specific or transferable to other proteins.

— PHASE: encoding global protein ensembles with local Hamiltonians and all-atom backmapping  (2608.23490 - Angioletti et al., 24 Aug 2026) in Section 1, Supplementary Information, immediately following Supplementary Fig.\ref{fig:supp_fapog_cutoff_sweep}