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

Akifumi Oda, Ken Saijo, Chikashi Ishioka, Koichi Narita, Tadashi Katoh, Yurie Watanabe, Shuichi Fukuyoshi, Ohgi Takahashi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalJournal of Molecular Graphics and Modelling
Volume54
DOIs
Publication statusPublished - 2014 Nov

Keywords

  • Computational docking
  • Dual inhibitor
  • Molecular dynamics simulation
  • Molecular superposition
  • Phosphoinositide 3-kinase
  • Romidepsin

ASJC Scopus subject areas

  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this