Figure 3.

Computational study of -[Pro-Gly]- and -[PEGO]- linkers and a model homobivalent ligand to investigate the conformation, distance span of the linkers, and overall linker moiety. Part A (top left) shows a [PG]₉ repeat taking a 6₁₇-helical conformation. MD simulation of this conformation at 310 K shows a significant helical pattern in the entire sample set of 1000 conformations with length ranging from 15 to 29 Å. Part B (top right) shows the PEGO linker in a bent conformation at global minimum. As expected, the linker shows a high degree of flexibility in MD simulations, with distance span between two ends ranging from 4 to 18 Å. Part C (bottom) shows a hypothetical homobivalent ligand, with ruler above, to indicate the approximate distance span of different subunits. The distances calculated from the GPCR dimer study and the modeling of linkers correlate quite well with the binding data.