Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement
Fig 4
The proposed two-step model of miRNA loading into hAgo2: Selective binding followed by structural re-arrangement (highlighted by the cyan arrow).
The induced fit mechanism (marked by the upper right grey arrow) and the conformational selection mechanism (marked by the lower left grey arrow) are also presented to compare with the two-step model. Average transition times between the closed states, the open state and the partially open states are computed from ten independent 10-ms synthetic trajectories generated by sampling the transition probability matrix of the 480-microstate MSM (see S10 Fig for additional details). The detailed transition pathways from the closed states to the open state can be found in S11 Fig.