title: Investigation of the inhibitors of histone-lysine N-methyltransferase SETD2 for acute lymphoblastic leukaemia from traditional Chinese medicine.
abstract: Leukaemia is the leading cause of childhood malignancies. Recent research indicates that the SETD2 gene is associated with acute lymphoblastic leukaemia. This study aims to identify potential lead compounds from traditional Chinese medicine (TCM) using virtual screening for SET domain containing 2 (SETD2) protein against acute lymphoblastic leukaemia. Docking simulation was performed to determine potential candidates which obtain suitable docking poses in the binding domain of the SETD2 protein. We also performed molecular dynamics (MD) simulation to investigate the stability of docking poses of SETD2 protein complexes with the top three TCM candidates and a control. According to the results of docking and MD simulation, coniselin and coniferyl ferulate have high binding affinity and stable interactions with the SETD2 protein. Coniselin is isolated from the alcoholic extract of Comiselinum vaginatum Thell. Coniferyl ferulate can be isolated from Angelica sinensis, Poria cocos (Schw.) Wolf, and Notopterygium forbesii. Although S-adenosyl-L-homocysteine has more stable interactions with key residues in the binding domain than coniselin and coniferyl ferulate during MD simulation, the TCM compounds coniselin and coniferyl ferulate are still potential candidates as lead compounds for further study in the drug development process with the SETD2 protein against acute lymphoblastic leukaemia.
authors.affiliation: a Department of Bioinformatics and Medical Engineering , Asia University , Taichung , Taiwan.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Chang
authors.affiliation: a Department of Bioinformatics and Medical Engineering , Asia University , Taichung , Taiwan.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chen
authors.affiliation: a Department of Bioinformatics and Medical Engineering , Asia University , Taichung , Taiwan.|b School of Medicine , College of Medicine, China Medical University , Taichung , Taiwan.|c Department of Anesthesiology , China Medical University Hospital , Taichung , Taiwan.
authors.forename: K-B
authors.initials: KB
authors.lastname: Chen
authors.affiliation: d School of Pharmacy , China Medical University , Taichung , Taiwan.
authors.forename: K-C
authors.initials: KC
authors.lastname: Chen
authors.affiliation: a Department of Bioinformatics and Medical Engineering , Asia University , Taichung , Taiwan.|e Department of Pharmacy , China Medical University Hospital, China Medical University , Taichung , Taiwan.
authors.forename: K-L
authors.initials: KL
authors.lastname: Chang
authors.affiliation: a Department of Bioinformatics and Medical Engineering , Asia University , Taichung , Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Chang
authors.affiliation: f School of Post-Baccalaureate Chinese Medicine , College of Chinese Medicine, China Medical University , Taichung , Taiwan.|g Department of Chinese Pediatrics , China Medical University Hospital , Taichung , Taiwan.
authors.forename: T-T
authors.initials: TT
authors.lastname: Chang
authors.affiliation: a Department of Bioinformatics and Medical Engineering , Asia University , Taichung , Taiwan.|h Research Center for Chinese Medicine and Acupuncture , China Medical University , Taichung , Taiwan.|i Department of Medical Research , China Medical University Hospital , Taichung , Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D052117:Benzodioxoles / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D003373:Coumaric Acids / Q000737:chemistry; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008516:Medicine, Chinese Traditional; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D052117:Benzodioxoles; D003373:Coumaric Acids; D004365:Drugs, Chinese Herbal; C000615775:coniselin; D011495:Histone-Lysine N-Methyltransferase
keywords: Leukaemia; histone-lysine N-methyltransferase SET domain containing 2 (SETD2); molecular dynamics (MD); traditional Chinese medicine (TCM); virtual screening