A QM/MM study of the binding of RAPTA ligands to cathepsin B

We have carried out quantum mechanical (QM) and QM/MM (combined QM and molecular mechanics) calculations, as well as molecular dynamics (MD) simulations to study the binding of a series of six RAPTA (Ru(II)-arene-1,3,5-triaza-7-phosphatricyclo-[3.3.1.1] decane) complexes with different arene substituents to cathepsin B. The recently developed QM/MM-PBSA approach (QM/MM combined with Poisson–Boltzmann solvent-accessible surface area solvation) has been used to estimate binding affinities. The QM calculations reproduce the antitumour activities of the complexes with a correlation coefficient (r ²) of 0.35–0.86 after a conformational search. The QM/MM-PBSA method gave a better correlation (r ² = 0.59) when the protein was fixed to the crystal structure, but more reasonable ligand structures and absolute binding energies were obtained if the protein was allowed to relax, indicating that the ligands are strained when the protein is kept fixed. In addition, the best correlation (r ² = 0.80) was obtained when only the QM energies were used, which suggests that the MM and continuum solvation energies are not accurate enough to predict the binding of a charged metal complex to a charged protein. Taking into account the protein flexibility by means of MD simulations slightly improves the correlation (r ² = 0.91), but the absolute energies are still too large and the results are sensitive to the details in the calculations, illustrating that it is hard to obtain stable predictions when full flexible protein is included in the calculations.     

An XPS investigation on glucose oxidase and Ni/Al hydrotalcite interaction

In this work, a Ni/Al hydrotalcite (HT) was used as glucose oxidase (GOx) immobilizer. Small‐area and angle‐resolved X‐ray photoelectron spectra were recorded on HTs electrosynthesized on Pt in the absence and in the presence of GOx, and compared with those obtained for a Pt surface, modified with the electrosynthesized HT, on which a drop of GOx solution was deposited. The simultaneous electrodeposition of HT + GOx resulted in a compact deposit, thicker than the XPS sampling depth (>10 nm), that is not homogeneous in the lateral and in‐depth composition. The presence of GOx can be deduced comparing the N1s spectra of HT and HT + GOx: in the latter, the N1s component at 400 eV binding energy (BE) is predominant whilst, depending on the analyzed point, a small or no contribution from the component at 407.2 eV, due to nitrate, is revealed. Angle‐resolved XPS provides evidence on the in‐depth composition of anions, cations and GOx. The results highlight the crucial role played by nickel in GOx immobilization. On the basis of the results, it can be suggested that enzyme activity is unevenly distributed and is localized in small areas, where Ni concentration is higher. Copyright © 2010 John Wiley & Sons, Ltd.     

Three-dimensional Wigner-function description of the quantum free-electron laser

A free-electron laser (FEL) operating in the quantum regime can provide a compact and monochromatic x-ray source. Here we present the complete quantum model for a FEL with a laser wiggler in three spatial dimensions, based on a discrete Wigner-function formalism taking into account the longitudinal momentum quantization. The model describes the complete spatial and temporal evolution of the electron and radiation beams, including diffraction, propagation, laser wiggler profile and emittance effects. The transverse motion is described in a suitable classical limit, since the typical beam emittance values are much larger than the Compton wavelength quantum limit. In this approximation we derive an equation for the Wigner function which reduces to the three-dimensional Vlasov equation in the complete classical limit. Preliminary numerical results are presented together with parameters for a possible experiment.     

Syntheses,Characterization, and DNA Binding Studies of a Series of Copper(II), Nickel(II), Platinum(II) and Zinc(II) Complexes Derived from Schiff Base Ligands

Three series of metal salophen complexes derived from Zn²⁺, Cu²⁺, Pt²⁺ and Ni²⁺ have been synthesized and their interaction with quadruplex DNA has been evaluated. The compounds differ on the number of ethyl piperidine substituents. They have been characterized by ¹H NMR, IR and UV-visible spectroscopies and by HR-mass spectrometry. Their luminescent properties have been also evaluated and we can observe that, as expected, Zn²⁺ and Pt²⁺ complexes are those displaying more interesting luminescence with an emission band red-shifted with respect to the corresponding uncoordinated ligand. DNA interactions with G4 and duplex DNA were evaluated by FRET melting assays (for the Zn²⁺, Cu²⁺ and Ni²⁺ complexes) and by emission titrations (for one Pt²⁺ complex) which indicated that the disubstituted compounds 2-Ni and 2-Pt are the only ones that display good affinity for G4 DNA structures.