InsiliCoil: An Integrated Software Suite for Coiled Coil Design, Prediction, and Therapeutic Engineering

Helical protein–protein interactions underpin transcriptional regulation, signal transduction, and self-assembly, yet their rational design remains challenging. Coiled coils (CCs) are particularly attractive as modular, programmable building blocks in synthetic biology, while also serving as therapeutic targets. Here we present InsiliCoil, a cross-platform software suite that unifies predictive modeling, selective peptide inhibitor discovery, and orthogonal interactome design into a single accessible framework. At its core, isCAN enables high-throughput identification of selective CC inhibitors, while CCIS systematically constructs orthogonal CC networks for synthetic biological circuits and biomaterials. Additional utilities support automatic heptad detection, heptad scanning, constraint analysis, charge block prediction, library generation, and large-scale visualization. Benchmarking against experimental data sets confirms that InsiliCoil reliably recovers validated inhibitors and interactomes, while offering orders-of-magnitude faster throughput than structure-based approaches. By providing a cohesive, user-friendly platform for controlling helix-mediated PPIs, InsiliCoil accelerates both therapeutic discovery and the rational engineering of programmable biological systems.