Markov state modeling
(MSM) for SAA1.1, the SAA1.1–hyaluronic
acid complex, and the SAA2.2–hyaluronic acid complex identifies
nine metastable states characterized by contact between linker I,
linker III, helix I, and helix III. (A) Time-lagged independent component
analysis (TICA) plot with microstates is shown in the left-hand panel.
Microstates from k-means clustering are plotted with
dots. The microstates are clustered into nine metastable states (I,
light sea-green; II, olive; III, deep sky-blue; IV, aqua; V, lime;
VI, medium sea-green; VII, dodger-blue; VIII, light sky-blue, and
IX, blue). An illustration of linker I, linker III, helix I, and helix
III is shown in the right-hand panel. (B) Representative structures
of each metastable state. N-terminus, pink; linker I, marine; linker
III, orange. (C) Interface and hyaluronic acid (green sticks) binding
site for groups 3 and 4 of SAA1.1.