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QMCube (QM3) is a suite written in the Python programming language, initially focused on multiscale QM/MM simulations of biological systems, but open enough to address other kinds of problems. It allows the user to combine highly efficient QM and MM programs, providing unified access to a wide range of computational methods. The suite also supplies additional modules with extra functionalities. These modules facilitate common tasks such as performing the setup of the models or process the data generated during the simulations. The design of QM3 has been carried out considering the least number of external dependencies (only an algebra library, already included in the distribution), which makes it extremely portable. Also, the modular structure of the suite should help to expand and develop new computational methods. [ABSTRACT FROM AUTHOR]

CYP19A1 aromatase is a member of the Cytochrome P450 family of hemeproteins, and is the enzyme responsible for the final step of the androgens conversion into the corresponding estrogens, via a three-step oxidative process. For this reason, the inhibition of this enzyme plays an important role in the treatment of hormone-dependent breast cancer. The first catalytic subcycle, corresponding to the hydroxilation of androstenedione, has been proposed to occur through a first hydrogen abstraction and a subsequent oxygen rebound step. In present work, we have studied the mechanism of the first catalytic subcycle by means of hybrid quantum mechanics/molecular mechanics methods. The inclusion of the protein flexibility has been achieved by means of Free Energy Perturbation techniques, giving rise to a free energy of activation for the hydrogen abstraction step of 13.5 kcal/mol. The subsequent oxygen rebound step, characterized by a small free energy barrier (1.5 kcal/mol), leads to the hydroxylated products through a highly exergonic reaction. In addition, an analysis of the primary deuterium kinetic isotopic effects, calculated for the hydrogen abstraction step, reveals values (∼10) overpassing the semiclassical limit for the CH, indicating the presence of a substantial tunnel effect. Finally, a decomposition analysis of the interaction energy for the substrate and cofactor in the active site is also discussed. According to our results, the role of the enzymatic environment consists of a transition state stabilization by means of dispersive and polarization effects. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The electronic structure of iron-oxo porphyrin π-cation radical complex Por·+FeIVO (SH) has been studied for doublet and quartet electronic states by means of two methods of the quantum chemical topology analysis: electron localization function (ELF) η( r) and electron density ρ( r). The formation of this complex leads to essential perturbation of the topological structure of the carbon-carbon bonds in porphyrin moiety. The double CC bonds in the pyrrole anion subunits, represented by pair of bonding disynaptic basins V i=1,2(C,C) in isolated porphyrin, are replaced by single attractor V(C,C) i=1-20 after complexation with the Fe cation. The iron-nitrogen bonds are covalent dative bonds, N→Fe, described by the disynaptic bonding basins V(Fe,N) i=1-4, where electron density is almost formed by the lone pairs of the N atoms. The nature of the iron-oxygen bond predicted by the ELF topological analysis, shows a main contribution of the electrostatic interaction, Feδ+···Oδ−, as long as no attractors between the C(Fe) and C(O) core basins were found, although there are common surfaces between the iron and oxygen basines and coupling between iron and oxygen lone pairs, that could be interpreted as a charge-shift bond. The FeS bond, characterized by the disynaptic bonding basin V(Fe,S), is partially a dative bond with the lone pair donated from sulfur atom. The change of electronic state from the doublet ( M = 2) to quartet ( M = 4) leads to reorganization of spin polarization, which is observed only for the porphyrin skeleton (−0.43e to 0.50e) and SH bond (−0.55e to 0.52e). © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]