Identification of Potential Allosteric Site Binders of Indoleamine 2,3-Dioxygenase 1 from Plants: A Virtual and Molecular Dynamics Investigation.

Ligand and structure-based computational screenings were carried out to identify flavonoids with potential anticancer activity. Kushenol E, a flavonoid with proven anticancer activity and, at the same time, an allosteric site binder of the enzyme indoleamine 2,3-dioxygenase-1 (IDO1), was used as the reference compound. Molecular docking and molecular dynamics simulations were performed for the screened flavonoids with known anticancer activity. The following two of these flavonoids were identified as potential inhibitors of IDO1: dichamanetin and isochamanetin. Molecular dynamics simulations were used to assess the conformational profile of IDO1-flavonoids complexes, as well as for calculating the bind-free energies.