substantiates our reasoning that the stability of the complex was mainly driven by π-π stacking interactions. Subsequently, we docked the Tetralin substrate in the so modified cage. After a few rounds of subsequent modifications that preserve the stability of HM1 and the binding of the substrate during simulations (see SI, Figure , S3, S4 & S5), we eventually achieved our final 'modeled cage' is shown in Figure . Here violet color shows modifications to stabilize HM1, while green represents the requisite modifications that stabilize the substrate binding.