SPARC sorts through vast amounts of sequence and structural data to identify the most statistically striking residue constraints. Based on BPPS, SIPRIS and direct coupling analyses, it estimates the statistical significance of the correspondence between high scoring residue pairs and interactions internal to a domain or at homomeric and heteromeric interfaces. And, given molecular dynamics simulated structures, it characterizes interactions among constrained residues or between such residues and ligands that are stably maintained during the simulation, undergo correlated formation and/or disruption, or switch between alternative interactions.