title: ILP-2 modeling and virtual screening of an FDA-approved library:a possible anticancer therapy.
abstract: OBJECTIVE
  The members of the inhibitors of apoptosis protein (IAP) family inhibit diverse components of the caspase signaling pathway, notably caspase 3, 7, and 9. ILP-2 (BIRC-8) is the most recently identified member of the IAPs, mainly interacting with caspase 9. This interaction would eventually lead to death resistance in the case of cancerous cells. Therefore, structural modeling of ILP-2 and finding applicable inhibitors of its interaction with caspase 9 are a compelling challenge.
  
  
  METHODS
  Three main protein modeling approaches along with various model refinement measures were harnessed to achieve a reliable 3D model, using state-of-the-art software. Thereafter, the selected model was employed to perform virtual screening of an FDA approved library.
  
  
  RESULTS
  A model built by a combinatorial approach (homology and ab initio approaches) was chosen as the best model. Model refinement processes successfully bolstered the model quality. Virtual screening of the compound library introduced several high affinity inhibitor candidates that interact with functional residues of ILP2.
  
  
  CONCLUSIONS
  Given the 3D structure of the ILP2 molecule, we found promising inhibitory molecules. In addition to high affinity towards the ILP2 molecule, these molecules interact with residues that play pivotal rules in ILP2-caspase interaction. These molecules would inhibit ILP2-caspase interaction and consequently would lead to reactivated cell apoptosis through the caspases pathway.
authors: Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Saeed
authors: S
authors: Khalili
authors: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Hemn
authors: H
authors: Mohammadpour
authors: Students' Research Committee, Semnan University of Medical Sciences, Semnan, Iran.
authors: Mahideh
authors: M
authors: Shokrollahi Barough
authors: Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK),Karolinska University Hospital Solna and Karolinska Institute, Stockholm, Sweden.
authors: Parviz
authors: P
authors: Kokhaei
mesh_terms: D000970:Antineoplastic Agents; D017209:Apoptosis; D020169:Caspases; D051034:Inhibitor of Apoptosis Proteins; D054852:Small Molecule Libraries; D014481:United States; D014486:United States Food and Drug Administration; D051636:X-Linked Inhibitor of Apoptosis Protein
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D054852:Small Molecule Libraries; D051636:X-Linked Inhibitor of Apoptosis Protein; D020169:Caspases
keywords: BIRC-8; Robetta; apoptosis; modeling