Thermal shift assay: Strengths and weaknesses of the method to investigate the ligand-induced thermostabilization of soluble guanylyl cyclase.

•Thermal Shift Assay determines sGC’s melting temperature with high reproducibility.•Method parameters were adjusted for measurement of sGC.•The method can be applied on sGC independent from heme content and heme state.•Activity-based thermostability measurement is useful to validate dye-based results.•Activity-based measurements are superior in detecting stabilization by activator drugs.