Lipid Receptor S1P1 Activation Scheme Concluded from Microsecond All-Atom Molecular Dynamics Simulations
Figure 2
Rotamer switches at S1P1 extracellular region.
(A) Apo S1P1, the χ1 angle of Y982.57 changed at 100 ns while W2696.48 and F2656.44 were stable during the whole simulation; (B, B′) antagonist ML056/S1P1, the χ1 angle of Y982.57 changed at 550 ns (or 300 ns in 2nd simulation); the χ2 of W2696.48 fluctuated in the initial 500 ns of simulation and it was stable in 2nd simulation; F2656.44 was stable in both simulation with antagonist; (C, C′) agonist S1P/S1P1, the χ1 angle of Y982.57 was relatively stable while both the χ2 angle of W2696.48 and χ1 of F2656.44 fluctuated considerably during the simulations. Internal water molecules are shown as pink dots. The initial structures of complexes after equilibration are shown in grey, while the final structures are shown in color. Blue dashed ellipse indicates lack of a flip of residue Y982.57 in case of complex with agonist.