Computational modelling of the binding of arachidonic acid to the human monooxygenase CYP2J2

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• 作者：G. Proietti ; K. K. Abelak ; D. Bishop-Bailey…
• 关键词：CYP2J2 ; Arachidonic acid ; Homology model ; Induced fit docking ; Molecular dynamics
• 刊名：Journal of Molecular Modeling
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：22
• 期：11
• 全文大小：4,619 KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023
• 卷排序：22

文摘

An experimentally determined structure for human CYP2J2—a member of the cytochrome P450 family with significant and diverse roles across a number of tissues—does not yet exist. Our understanding of how CYP2J2 accommodates its cognate substrates and how it might be inhibited by other ligands thus relies on our ability to computationally predict such interactions using modelling techniques. In this study we present a computational investigation of the binding of arachidonic acid (AA) to CYP2J2 using homology modelling, induced fit docking (IFD) and molecular dynamics (MD) simulations. Our study reveals a catalytically competent binding mode for AA that is distinct from a recently published study that followed a different computational pipeline. Our proposed binding mode for AA is supported by crystal structures of complexes of related enzymes to inhibitors, and evolutionary conservation of a residue whose role appears essential for placing AA in the right site for catalysis.