Scoulerine is a natural compound that is known to bind to
tubulin and has anti-mitotic properties demonstrated in various
cancer cells. Its molecular mode of action has not been precisely known. In this work, we perform computational prediction and experimental validation of the mode of action of
scoulerine. Based on the existing data in the
Protein Data Bank (PDB) and using homology modeling, we create human
tubulin structures corresponding to both free
tubulin dimers and
tubulin in a microtubule. We then perform docking of the optimized structure of
scoulerine and find the highest affinity binding sites located in both the free
tubulin and in a microtubule. We conclude that binding in the vicinity of the
colchicine binding site and near the
laulimalide binding site are the most likely locations for
scoulerine interacting with
tubulin. Thermophoresis assays using
scoulerine and
tubulin in both free and polymerized form confirm these computational predictions. We conclude that
scoulerine exhibits a unique property of a dual mode of action with both microtubule stabilization and
tubulin polymerization inhibition, both of which have similar affinity values.