A multiscale approach to modelling drug metabolism by membrane-bound cytochrome P450 enzymes.

ABSTRACT: Cytochrome P450 enzymes are found in all life forms. P450s play an important role in drug metabolism, and have potential uses as biocatalysts. Human P450s are membrane-bound proteins. However, the interactions between P450s and their membrane environment are not well-understood. To date, all P450 crystal structures have been obtained from engineered proteins, from which the transmembrane helix was absent. A significant number of computational studies have been performed on P450s, but the majority of these have been performed on the solubilised forms of P450s. Here we present a multiscale approach for modelling P450s, spanning from coarse-grained and atomistic molecular dynamics simulations to reaction modelling using hybrid quantum mechanics/molecular mechanics (QM/MM) methods. To our know

SUBMITTER: Lonsdale R 

PROVIDER: S-EPMC4102395 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature