SERCA 2A is the dominant isoform found in cardiac muscle, and thus plays a large role in cardiac relaxation and calcium handling . SERCA 2A dysfunction has been linked to pathogenesis in the heart and elsewhere, and SERCA has also been investigated as a therapeutic target . A recent computational study investigated the effects of 2'-deoxy-ATP (dATP), a small molecule analog of ATP, on SERCA . dATP is a potential small molecule therapeutic for treating heart failure, and has been shown to improve contractile function in the heart by acting on myosin, a motor protein largely responsible for cardiac contraction . dATP has also been shown to speed reuptake of calcium into the SR, leading to improved cardiac relaxation . Hock et al. showed that this could be at least partially explained by dATP binding and activating the SERCA pump in place of ATP . This study found that dATP formed more stable contacts in the nucleotide binding pocket than ATP, leading to enhanced A-N domain closure and an increase in the calcium association rate via opening of the calcium binding pathway. However, it is unclear how changes in the cytosolic region due to dATP binding lead to conformational and functional changes in the transmembrane calcium binding region. The M5 helix has been shown to mechanically couple the calcium and nucleotide binding sites , but it is unknown how dATP affects this or if other connection pathways exist. Therefore, MI provides a useful tool for investigating how conformational changes to the protein following dATP binding propagate to changes in calcium association.