An ab Initio Approach to the Understanding of
Cytochrome P450 - Ligand Interactions
Abstract
- We describe the application of novel ab initio quantum
mechanical methods to the study of ligand interactions with cytochrome
P450cam.
- We find that our techniques accurately describe the transition
from a low-spin state to a high-spin state of the haem Fe3+ on binding
of a substrate. Furthermore, our methods correctly predict that a
large fraction of low-spin character is retained on binding of an
inhibitor.
- We demonstrate the use of `computational experiments' to
elucidate key features of the mechanism of interaction. This leads us
to identify a new mechanism for the suppression of the low- to
high-spin transition on binding of an inhibitor, namely the shortening
of the bond between the Fe atom and the coordinated S atom of the
cysteine axial ligand.
A full version of this paper can be downloaded in gzipped postscript. If you wish to receive
a paper copy, please email me.
Matthew Segall (mds21@phy.cam.ac.uk)
Last modified: Tue Apr 6 14:02:14 1999