  We study the binding of plant hormone IAA on its receptor TIR1 introducing a
novel computational method that we call tomographic docking and that accounts
for interactions occurring along the depth of the binding pocket. Our results
suggest that selectivity is related to constraints that potential ligands
encounter on their way from the surface of the protein to their final position
at the pocket bottom. Tomographic docking helps develop specific hypotheses
about ligand binding, distinguishing binders from non-binders, and suggests
that binding is a three-step mechanism, consisting of engagement with a niche
in the back wall of the pocket, interaction with a molecular filter which
allows or precludes further descent of ligands, and binding on the pocket base.
Only molecules that are able to descend the pocket and bind at its base allow
the co-receptor IAA7 to bind on the complex, thus behaving as active auxins.
Analyzing the interactions at different depths, our new method helps in
identifying critical residues that constitute preferred future study targets
and in the quest for safe and effective herbicides. Also, it has the potential
to extend the utility of docking from ligand searches to the study of processes
contributing to selectivity.
