Fig 1. Overview of modeled kinetic transitions.

Our computational model combines two three-state cycles to simulate activation of thin-filament regulatory units (r_t,ij) and the cycling of cross-bridges (r_x,ij). Thin-filament activation is described by an initial state where calcium is unbound from the troponin complex and tropomyosin blocks the actin-target zone (TF1), a second state where calcium is bound to troponin but tropomyosin remains in a blocking conformation (TF2), and a final state where the calcium activation of troponin shifts tropomyosin and reveals the actin-target zone (TF3). Following TF3, cross-bridge binding occurs in three states: an initial unbound state (XB1), a low-force bearing, pre-power stroke state (XB2), and a high-force bearing, post-power stroke state (XB3).