First Principles Calculation of the Activity of Cytochrome P450
The cytochrome P450 superfamily of enzymes is of enormous interest in
the biological sciences due to the wide range of endogenous and
xenobiotic compounds which it metabolises, including many drugs. We
describe the use of first principles quantum mechanical modeling
techniques, based on Density Functional Theory, to determine the
outcome of interactions between an enzyme and a number of
compounds. Specifically, we calculate the spin state of an Fe3+ ion
present in a haem moiety at the active site of these enzymes. The spin
state of this ion indicates if the catalytic reaction will
proceed. The computational results obtained compare favourably with
experimental data. Only the principle components of the active site of
the enzyme are included in the computational models, demonstrating
that only a small fragment of the protein needs to be included in the
models in order to accurately reproduce this aspect of the enzymes'
function. These results open the way for further investigation of this
superfamily of enzymes using the methods detailed in this paper.
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 (firstname.lastname@example.org)
Last modified: Fri Aug 29 16:35:13 1997