Fig. 6.

Binding pathways of the Numb RNA to the MSI1 protein revealed from GaMD simulations: Starting from free diffusion in the solvent, the Numb RNA spontaneously bound to the target site of the MSI1 via intermediate conformations in the (A) “Sim1”, (B) “Sim2”, (C) “Sim3”, (D) “Sim4”, (E) “Sim5” and (F) “Sim6” GaMD trajectories. In the intermediate conformations, the Numb RNA interacted with the C-terminus (A, C, E and F), the β2-β3 loop (D) or both the C-terminus and β2-β3 loop (B) of MSI1. The MSI1 protein is shown in blue ribbons. The Numb RNA structural clusters (sticks) are colored by the reweighted PMF free energy values in a green (0.0 ​kcal/mol)-white-red (2.0 ​kcal/mol) color scale.