Binder residues at sites Iα, Iβ, and II. (A) Distances between the binder residues and the LIN (blue) and STE (purple) constant binders at site Iα are displayed across the 5-µs simulation period. (B and C) Same as in A but for site Iβ and site II, respectively. Variations in fluctuations across the distance measurements of the residues interacting with the STE and LIN constant binders are especially evident for the hydrophobic residues stabilizing the FA tails. In particular, the STE constant binders are unable to maintain a close interaction with the S5 residues Y268 and L272 in the site Iα (A). Overall, the lack of tail flexibility in STE and the stiffness of its tail prevents this saturated FA from interacting as efficiently as the more mobile unsaturated tail of LIN with the network of hydrophobic residues at site I or to fit into the more restricted cavity at site II.