Aromatáz – running

The human aromatase enzyme is a member of the P450 superfamily and it plays important role in the biosynthesis of estrogens (estrone and estradiol) in the human body. This enzyme catalyzes a mutistep process, in which the substrate molecule (androstenedione or testosterone) binding in the active site becomes oxidatively demethylized between the ring A and ring B of the sterane structure. Because of this transformation the ring A becomes aromatic.
Our aim is the investigation of the most important steps of the mechanism of the enzyme catalysed chemical transformation by quantum mechanical (QM) and combined quantum mechanical and molecular mechanical methods. We are interested in the enolisation process of the androstenedione because this transformation is essential for the lowering energy barriers of the next reaction steps. We would like to investigate the other reaction steps too, which contain abstraction of hydrogen radical and rebound of hydroxyl radical. These steps are important parts of the general mechanism of the P450 enzymes.
The first exercise is the preparation of the protein model using molecular mechanical methods for the classical molecular dynamical simulations. We can generate several suitable starting structures with MD simulations for the QM/MM simulations. We will use so called adiabatic mapping, in which we can simulate the chemical transformation by using a suitable reaction coordinate. This reaction coordinate means an extra geometrical condition for the minimisation of the energy of the system and we can make the system transform from the reactant state to the product state. The obtained data allow us of describe the features of the system sophisticatedly.

Project owner:
Krámos Balázs (Szervetlen és Analitikai Kémia Tanszék)
Szervetlen és Analitikai Kémia Tanszék (VBK-IAACHEM)