Investigation of substrate recognition for cytochrome P450 1A2 mediated by water molecules using docking and molecular dynamics simulations

Yurie Watanabe, Shuichi Fukuyoshi, Koichi Kato, Masahiro Hiratsuka, Noriyuki Yamaotsu, Shuichi Hirono, Hiroaki Gouda, Akifumi Oda

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The role of water molecules in the active site of cytochrome P450 1A2 (CYP1A2) was investigated using an explicit water model to simulate biological environments. Moreover, differences in ligand recognition between the inhibitor α-naphthoflavone (ANF) and the substrate 7-ethoxyresorufin (7ER) in the CYP1A2 complex were examined. More than 200-ns molecular dynamics (MD) simulations were performed for each complex structure of CYP1A2. In the complex structure with 7ER obtained after MD simulation, some water molecules existed in the active site and formed hydrogen bonds between 7ER and some residues. However, in the complex structure with ANF, the hydrogen bond network differed. These results suggest that CYP1A2 requires water molecules in its active site for substrate recognition. The observed differences in the hydrogen bond network in the complex with ANF or 7ER may be due to the fact that ANF is an inhibitor.

Original languageEnglish
Pages (from-to)326-336
Number of pages11
JournalJournal of Molecular Graphics and Modelling
Volume74
DOIs
Publication statusPublished - 2017 Jun 1

Keywords

  • CYP1A2
  • Docking
  • Ligand recognition
  • Molecular dynamics
  • Water

ASJC Scopus subject areas

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

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