It is interesting to note that when the DCM-causing mutation K36Q in cTnI was introduced in the presence of Ca2+, the simulation showed that Ser 22 and 23 no longer interacted closely with cTnC, in accord with our hypothesis that the Ca2+-cTnC-cTnI N terminus interaction is unique and is destabilized directly by phosphorylation and also allosterically by mutations and other perturbations. This evidence concerns the gene TNNI3 and familial dilated cardiomyopathy.