Headgroup Interaction Prevalence (HIP) analysis: We took all the probe residence reactions and measured, at each time-step, the minimal distance of each of the probe's headgroup moieties to other moiety types in the cluster. If the distance was equal or below 0.3nm, we noted that the moieties interaction is present. For each reaction, we calculated the fraction of the residence time in which each possible probe-cluster moieties interaction occurs (HIP values). Then, we grouped the reactions into two groups based on the duration of their residence times -long residence group (above 10ns) and short residence group (1ns-2ns) -and calculated the average HIP value for every possible headgroup pair interactions within each group. Lastly, we calculated the fold changes in the HIP values between these two groups for each moiety pair interaction, as a ratio of the long residence group over the short residence group. T-tests were applied to observe the significance of the fold changes Dynamic Headgroup Interaction Prevalence (HIP) analysis: We first divided all reactions into two groups based on their involved clusters composition (below 50%, and above 50% lipid modulator levels). Then, we calculated the presence of a probe-cluster moiety interaction across all compatible reactions in a specific group, and did so separately for each relevant time-step (for the first and last 0.5ns of residence time). The HIP trends were smoothed with a sliding window of 10ps. Later, we calculated the difference (shift) in the HIP plots between the modulator-rich and modulator-poor groups. We did so only for cross-interactions (between lipids of different types), since same-type interactions exist in clusters of many additional lipid types and thus are not applicable to this analysis.