Exploring peroxides detoxification reactions using QM/MM simulation tools

Life on Earth evolved in the presence of hydrogen peroxide, and other peroxides also emerged
before and with the rise of aerobic metabolism. They were considered only as toxic byproducts
for many years. Nowadays, peroxides are also regarded as metabolic products that play
essential physiological cellular roles. In addition, peroxides play a key role in many
biotechnological processes. Organisms have developed efficient mechanisms to detoxify
peroxides, mostly based on two kinds of redox chemistry, catalases/peroxidases that depend
on a heme prosthetic group to afford peroxide reduction and thiol-based peroxidases that
support their redox activities on specialized fast reacting cysteine/selenocysteine (Cys/Sec)
residues. In this seminar, I will present a multi scale computer simulation approach, in which
classical and quantum-classical (QM-MM) at the density functional level simulations using our
group LIO code, are employed to explore the molecular basis of peroxides detoxification, in
close synergy with experimental measurements. Specifically I will show results concerning :
1) the differential reactivity of low molecular weight thiols with hydrogen peroxide and
peroxynitrite. 2) the paradigmatic case of the peroxiredoxin of Mycobacterium Tuberculosis
called AhPE reactivity towards hydrogen peroxide and fatty acid peroxides. 3) an analysis of
the reactivity of persulfides and selenides of low molecular weight, compared to the thiol
analogs in order to shed light on the potential function of this naturally occurring substitutions.
4) the molecular basis of the reactivity of hydrogen peroxides with heme proteins, such as
myoglobin and horse radish peroxidase