Probe Orientation analysis: The orientation of a lipid is defined as the angle between two vectors -the lipid vector, that connects a prominent atom in the lipid's headgroup and its terminal carbon, and the vector that connects the lipid headgroup and the geometrical center of the involved cluster. The prominent headgroups atoms are: "N" for DPC, "S" for SDS, "N" for DDA, "S" for DAS, and the carboxyl "C1" for LAU. The probe orientations were calculated for all the residence reactions from the exit analysis, and separately for each timestep within the first and last 0.5ns. The plots were smoothed with a sliding window of 10ps. Similar to the dynamic HIP analysis, the residence reactions were divided into two groups based on the involved cluster composition (below 50%, and above 50% lipid modulator levels). Afterwards, all compatible reactions within each group were averaged discreetly for each time-step, generating a typical orientation progression for the group. Lastly, we calculated the difference (shift) in the probe orientation plots between the modulator-rich and modulator-poor groups.