Figure 3.

CBD simulation results. The CBD simulation results allow us to compute the effects of linker length on the ability of IFN to bind to its receptors. (A) Exploration of space near the membrane by IFNα when the anti-CD20 scFv is bound to CD20. The green ellipse is the full space sampled by IFNα, the tan region is where it is possible for IFNα to bind to its receptors, and the purple region is the cell membrane. The shaded region is the intersection between the sampled space and the possible binding region. (B) Longer linkers increase the proportion of conformations where IFNα cannot bind. (C) Expanded diagram of the possible binding region, showing the conditions that affect the calculated likelihood of binding. The measure of the likelihood of binding in a given configuration takes into account both the distance of the IFNα binding site from the optimal height off the membrane, d, and the angular distance of binding site from its optimal orientation, θ. The CBD simulation computes the likelihood of binding at every step in time and aggregates the results to compute an overall binding likelihood measure for a given construct (in ABU). (D) The likelihood of binding in ABU as a function of linker length was calculated via CBD simulation. We ran 40 simulations, each 1 ms long, for each linker length. To see this figure in color, go online.