Recent progress on structural bioinformatics research of cytochrome P450 and its impact on drug discovery

Adv Exp Med Biol. 2015:827:327-39. doi: 10.1007/978-94-017-9245-5_19.

Abstract

Cytochrome P450 is predominantly responsible for human drug metabolism, which is of critical importance for drug discovery and development. Structural bioinformatics focuses on analysis and prediction of three-dimentional structure of biological macromolecules and elucidation of structure-function relationship as well as identification of important binding interactions. Rapid advancement of structural bioinformatics has been made over the last decade. With more information available for CYP structures, the methods of structural bioinformatics may be used in the CYP field. In this review, we demonstrate three previous studies on CYP using the methods of structural bioinformatics, including the investigation of reasons for decrease of enzymatic activity of CYP1A2 caused by a peripheral mutation, the construction of a pharmacophore model specific to active site of CYP1A2 and the prediction of the functional consequences of single residue mutation in CYP. By illustrating these studies we attempt to show the potential role of structural bioinformatics in CYP research and help better understanding the importance of structural bioinformatics in drug designing.

MeSH terms

  • Amino Acid Sequence
  • Computational Biology*
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Discovery*
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid

Substances

  • Cytochrome P-450 Enzyme System