TY - JOUR
T1 - 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
AU - Oda, Akifumi
AU - Saijo, Ken
AU - Ishioka, Chikashi
AU - Narita, Koichi
AU - Katoh, Tadashi
AU - Watanabe, Yurie
AU - Fukuyoshi, Shuichi
AU - Takahashi, Ohgi
N1 - Funding Information:
Parts of the computations were performed by the Research Center for Computational Science, Okazaki. This work was supported by a grant-in-aid for scientific research [ 23790137 ] from the Japan Society for the Promotion of Science .
Publisher Copyright:
© 2014 Elsevier Inc. All rights reserved.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Computational docking
KW - Dual inhibitor
KW - Molecular dynamics simulation
KW - Molecular superposition
KW - Phosphoinositide 3-kinase
KW - Romidepsin
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U2 - 10.1016/j.jmgm.2014.08.007
DO - 10.1016/j.jmgm.2014.08.007
M3 - Article
C2 - 25254927
AN - SCOPUS:84908287890
VL - 54
SP - 46
EP - 53
JO - Journal of Molecular Graphics and Modelling
JF - Journal of Molecular Graphics and Modelling
SN - 1093-3263
ER -