Table 1.

Challenges for modeling of CaMKII activity across scales from molecule to tissue.

Scale	Challenges for modeling	Representative models
Molecule	Regulation by Ca2+/calmodulin and post-translational modification (including autophosphorylation).	Hanson et al. (1994), Coomber (1998), Dupont et al. (2003), Gaertner et al. (2004).
	Complex structure/function relationship.	Lisman and Goldring (1988), Michelson and Schulman (1994), Zhabotinsky (2000), Kubota and Bower (2001), Miller et al. (2005), Lucic et al. (2008), Michalski (2013).
Cell	Dynamic Ca2+ signaling as input. Large number of substrates. Resides at center of vast signaling network.	Hund and Rudy (2004), Iribe et al. (2006), Grandi et al. (2007), Livshitz and Rudy (2007), Chiba et al. (2008), Saucerman and Bers (2008), Soltis and Saucerman (2010), Dupont et al. (2010), O’Hara et al. (2011).
	Chronic vs. acute effects of CaMKII activation.	Hund et al. (2008), Koivumaki et al. (2009), Hashambhoy et al. (2010), Lascano et al. (2013), Zang et al. (2013).
Tissue/organ	Chronic and acute remodeling in disease.	Christensen et al., 2009, Swaminathan et al., 2012, Luo et al., 2013.