Cytochrome P450s, the largest known super-family of proteins, are most abundant in the liver, where they are known to metabolize drugs and steroids.  Of the CYP2 subfamily, CYP2C9 is the most enantiospecific P450 based on metabolic studies; however, the molecular interactions which cause this difference are unknown.  To determine how the intermolecular forces differ between enantiomers and the CYP2C9 enzyme, a computational study of molecular dynamics simulations was conducted using Tripos Sybyl-X software to dock a series of chiral drugs into the CYP2C9 crystal structure.  The interactions between each ligand and the residues within CYP2C9 were identified, and the energy of each interaction was calculated.  These observed interactions and energies allowed for the docking affinity of each residue involved to be determined in order to show which residues contribute to CYP2C9 enantiospecificity.  The data obtained will add to future projects studying the broad effects of substrate chirality on metabolic activity.

Computational docking analysis of enantiospecificity in CYP2C9 drug metabolism

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.