Advisor Information
Haizhen Zhong
Location
Dr. C.C. and Mabel L. Criss Library
Presentation Type
Poster
Start Date
3-3-2017 10:45 AM
End Date
3-3-2017 12:00 PM
Abstract
Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: 2RD0), PI3Kβ (2Y3A), PI3Kγ (3IBE), PI3Kγ (1E8W), & PI3Kδ (2WXG) and to explore binding residues that may be responsible for isoform-selective binding. Our free energy estimation method was successful in predicting the ligand binding parameters (binding constants Kds or IC50s). Residues responsible for isoform-specific binding will be reported.
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons, Other Chemicals and Drugs Commons, Structural Biology Commons
Docking Studies of Isoform-Selectivity of Phosphatidylinositol 3-Kinase (PI3K) Inhibitors
Dr. C.C. and Mabel L. Criss Library
Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: 2RD0), PI3Kβ (2Y3A), PI3Kγ (3IBE), PI3Kγ (1E8W), & PI3Kδ (2WXG) and to explore binding residues that may be responsible for isoform-selective binding. Our free energy estimation method was successful in predicting the ligand binding parameters (binding constants Kds or IC50s). Residues responsible for isoform-specific binding will be reported.