Multiscale simulations of the effects of 2’-deoxy-ATP and a myosin mutation on actomyosin interactions

The actin-myosin cross-bridge cycle catalyzes the hydrolysis of ATP, leading to cardiomyocyte contraction. 2'-deoxy-ATP (dATP) is a myosin activator, which increases contractile force in cardiomyocytes even at relatively low concentrations of the adenine nucleotide pool. dATP has therefore been proposed as a therapeutic for heart failure with reduced ejection fraction. Previous studies have demonstrated that, compared with ATP, dATP induces conformational and electrostatic changes in myosin that increase the association rate of myosin to actin.