title: Predicting the structures of complexes between phosphoinositide 3-kinase (PI3K) and romidepsin-related compounds for the drug design of PI3K/histone deacetylase dual inhibitors using computational docking and the ligand-based drug design approach.
abstract: Predictions of the three-dimensional (3D) structures of the complexes between phosphoinositide 3-kinase (PI3K) and two inhibitors were conducted using computational docking and the ligand-based drug design approach. The obtained structures were refined by structural optimizations and molecular dynamics (MD) simulations. The ligands were located deep inside the ligand binding pocket of the p110α subunit of PI3K, and the hydrogen bond formations and hydrophobic effects of the surrounding amino acids were predicted. Although rough structures were obtained for the PI3K-inhibitor complexes before the MD simulations, the refinement of the structures by these simulations clarified the hydrogen bonding patterns of the complexes.
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan; Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan; Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita 565-0871, Osaka, Japan. Electronic address: oda@p.kanazawa-u.ac.jp.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Oda
authors.affiliation: Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku Sendai 980-8575, Miyagi, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Saijo
authors.affiliation: Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku Sendai 980-8575, Miyagi, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Narita
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Katoh
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fukuyoshi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Miyagi, Japan.
authors.forename: Ohgi
authors.initials: O
authors.lastname: Takahashi
mesh_terms: D047630:Depsipeptides / Q000737:chemistry*; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; C087123:romidepsin
keywords: Computational docking; Dual inhibitor; Molecular dynamics simulation; Molecular superposition; Phosphoinositide 3-kinase; Romidepsin