Figure 4: dATP Mechanism of Action

(A) Molecular simulation results show the loss of O2′ on dADP disrupts contacts in the nucleotide binding pocket on myosin. Representative structures showing conformational changes within the nucleotide binding pocket at 50 ns with ADP and dADP. Phe129 (magenta) and the primary contacts it makes are shown (dotted black lines). (B) Representative acting binding surface structures on myosin (circled area on ribbon structure) with ADP and dADP simulations at 50 ns, showing conformational changes in myosin resulting in increased exposure of polar residues (green regions) in the actin binding surface with dADP binding. Modeling figures adapted with permission from S.G. Nowakowski, M. Regnier, V. Daggett, unpublished data, October 2016. (C) Schematic illustrating the chemomechanical cycle of muscle contraction. Transitions between actin (A) and myosin (M) binding states are labeled. Transition states in boxes are where dATP alters the cycle, with the magnitude of the dATP effect indicated by the number of plus symbols.