title: Docking Studies and Molecular Dynamic Simulations Reveal Different Features of IDO1 Structure.
abstract: In the last decade, indoleamine 2,3-dioxygenase 1 (IDO1) has attracted a great deal of attention being recognized as key regulator of immunosuppressive pathways in the tumor immuno-editing process. Several classes of inhibitors have been developed as potential anticancer agents, but only few of them have advanced in clinical trials. Hence, the quest of novel potent and selective inhibitors of the enzyme is still active and mostly pursued by structure-based drug design strategies based on early and more recent crystal structures of IDO1. Combining docking studies and molecular dynamic simulations, in this work we have comparatively investigated the structural features of each crystal structure of IDO1. The results pinpoint different features in specific crystal structures of the enzyme that may benefit the medicinal chemistry arena aiding the design of novel potent and selective inhibitors of IDO1.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
authors.forename: Francesco Antonio
authors.initials: FA
authors.lastname: Greco
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
authors.forename: Answald
authors.initials: A
authors.lastname: Bournique
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Coletti
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Custodi
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dolciami
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carotti
authors.affiliation: Dipartimento di Scienze Farmaceutiche, University of Perugia, Via del Liceo 1, 06123, Perugia, Italy, . antonio.macchiarulo@unipg.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Macchiarulo
mesh_terms: D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D062105:Molecular Docking Simulation / Q000379:methods; D056004:Molecular Dynamics Simulation; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
keywords: Antibacterial; Antifungal; Antiviral; Cancer; Drug Design; IDO; Inhibitor; Tryptophan