Fig. 5: Molecular dynamics studies of the PI(3,4,5)P3 binding site.
From: Activation and substrate specificity of the human P4-ATPase ATP8B1
a Hydrogen bonding (H-bond) frequencies between protein and the PI(3,4,5)P3 (blue) and PI (purple) headgroup from the last 200 ns of five MD trajectories of each system. b, c Relative x, y, and z positions of the center of mass (COM) of the inositol ring to the COM of selected Cɑ atoms of cavity-lining protein residues used as reference (see e) showing different mobility of the PI(3,4,5)P3 (blue; b) and PI (purple; c) headgroups. The highlighted points and numbers correspond to the cluster centroids in e and M indicating the initial position of the PI(3,4,5)P3 molecule as modeled and refined in the cryo-EM map of the E2Pautoinhibited “closed” conformation. d Clustering of inositol ring coordinates from the last 200 ns of each trajectory for PI(3,4,5)P3 (blue) and PI (purple). e Structural visualization of the cluster centroids from clustering PI(3,4,5)P3 (blue) and PI (purple) inositol poses in the binding cavity (wheat). The inositol ring position as refined in the cryo-EM map of the E2Pautoinhibited “closed” with PI(3,4,5)P3 conformation is shown in green. Only centroids from clusters containing ≥5% of the clustered structures are shown.
