Extended Data Fig. 4: Enhanced sampling simulations of Pi release from the F-actin barbed end and core.
From: Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments
a, Representative egress paths from the barbed end show a clear preference for egress through the open R177-N111 backdoor. The F-actin structure fluctuated during the simulations but is shown in a single, representative conformation for clarity. b, Path cluster occupancies in barbed end simulations with the same color code as in panel a. c, A representative path of Pi egress through pathway 2 (purple) in F-actin core simulations. The simulation revealed a highly bent ADP conformer that allowed Pi to escape. Such a drastic rearrangement of the nucleotide binding pocket is physically implausible. In addition, this egress path would not be directly affected by phalloidin and jasplakinolide binding. Hence, this pathway was not considered for further experimental validation. d, A representative path of Pi egress through pathway 3 (magenta) in F-actin core simulations. This escape would also not be directly affected by phalloidin and jasplakinolide binding. Hence, it was not considered for further experimental validation. Similar to panel a, the F-actin structure is shown in a single, representative conformation for clarity. e, Path cluster occupancies in actin core simulations with the same color code as in Fig. 2. Pathways 1 and 4 are further discussed in the main text.
