Monoamine oxidases (MAOs) are flavoenzymes important in regulating amine neurotransmitter levels and are the central pharmacological targets in treating depression and Parkinson's disease. On the basis of quantum chemical calculations, we have proposed a new two‐step hydride mechanism for the MAO‐catalysed oxidative deamination of amines. In the rate‐limiting first step, through its N5 atom, the flavin abstracts a hydride anion from the substrate α‐carbon atom and forms a strong covalent adduct with the thus created cation. This is followed by flavin N1 deprotonation of the substrate amino group, facilitated with two active‐site water molecules, to produce fully reduced flavin, FADH2, and neutral imine. We have demonstrated that our mechanism is in agreement with available experimental data and provided evidence against both traditional polar nucleophilic and single‐electron radical pathways. These results provide valuable information for mechanistic studies on other flavoenzymes and for the design of new antidepressants and antiparkinsonian drugs.

Vibrational spectroscopy studies show that the bulk water bending band becomes narrower with increasing temperature (Maréchal, Y. J. Mol. Struct. 1994, 322, 105). Since this counterintuitive effect is not associated with the quantum nature of nuclear motion a molecular dynamics (MD) simulation is expected to reproduce it even in the classical limit. We have performed a classical MD simulation of the flexible simple point charge (SPC) and extended SPC (SPC/E) water models to determine the temperature dependence of the bulk water vibrational spectrum. The intramolecular water potential proposed by Toukan and Rahman, including a stretch−bend coupling term, was applied. We performed MD simulations at −4 and 80 °C to compare the calculated vibrational spectra, in particular, the band associated with the bending mode, with the experiment. The experimentally determined narrowing of the bending band with increasing temperature is not reproducible by MD simulation with the applied force field. However, the results show that this approach successfully reproduces all other experimentally observed spectroscopic properties of bulk water.

Predicting the endocrine disruption potential of compounds is a daunting but essential task. Here we report a new tool for this purpose that we have termed Endocrine Disruptome. It is a free and simple-to-use Web service that runs on an open source platform called Docking interface for Target Systems (DoTS). The molecular docking is handled via AutoDock Vina. Compounds are docked to 18 integrated and well-validated crystal structures of 14 different human nuclear receptors: androgen receptor; estrogen receptors α and β; glucocorticoid receptor; liver X receptors α and β; mineralocorticoid receptor; peroxisome proliferator activated receptors α, β/δ, and γ; progesterone receptor; retinoid X receptor α; and thyroid receptors α and β. Endocrine Disruptome is free of charge and available at http://endocrinedisruptome.ki.si.