Theory 01/Molecular/Drug binding
Residence Is Pocket Against Diffusion
The claim
Ligand residence time is set by the ratio of binding pocket volume to ligand diffusion coefficient, so a deep pocket slows escape more than tight binding does.
01Mechanism
Escape requires the ligand to find the exit; a larger pocket with the same affinity gives more chances to rebind before diffusing away.
02Prediction
Residence should track pocket volume at equal affinity.
03Refutation
Residence tracking affinity alone would remove the geometric term.