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Biomolecules with metal ion(s) (e.g., metalloproteins) play many important biological roles. However, accurate structural determination of metalloproteins, particularly those containing transition metal ion(s), is challenging due to their complicated electronic structure, complex bonding of metal ions, and high number of conformations in biomolecules. Quantum refinement, which was proposed to combine crystallographic data with computational chemistry methods by several groups, can improve the local structures of some proteins. In this study, a quantum refinement method combining several multiscale computational schemes with experimental (X-ray diffraction) information was developed for metalloproteins. Various quantum refinement approaches using different ONIOM (our own N-layered integrated molecular orbital and molecular mechanics) combinations of quantum mechanics (QM), semiempirical (SE), and molecular mechanics (MM) methods were conducted to assess the performance and reliability on the refined local structure in two metalloproteins. The structures for two (Cu- or Zn-containing) metalloproteins were refined by combining two-layer ONIOM2(QM1/QM2) and ONIOM2(QM/MM) and three-layer ONIOM3(QM1/QM2/MM) schemes with experimental data. The accuracy of the quantum-refined metal binding sites was also examined and compared in these multiscale quantum refinement calculations. ONIOM3(QM/SE/MM) schemes were found to give good results with lower computational costs and were proposed to be a good choice for the multiscale computational scheme for quantum refinement calculations of metal binding site(s) in metalloproteins with high efficiency. Additionally, a two-center ONIOM approach was employed to speed up the quantum refinement calculations for the Zn metalloprotein with two remote active sites/ligands. Moreover, a recent quantum-embedding wavefunction-in-density functional theory (WF-in-DFT) method was also adopted as the high-level method in unprecedented ONIOM2(CCSD-in-B3LYP/MM) and ONIOM3(CCSD-in-B3LYP/SE/MM) calculations, which can be regarded as novel pseudo-three- and pseudo-four-layer ONIOM methods, respectively, to refine the key Zn binding site at the coupled-cluster singles and doubles (CCSD) level. These refined results indicate that multiscale quantum refinement schemes can be used to improve the structural accuracy obtained for local metal binding site(s) in metalloproteins with high efficiency.

International audience; Influence of 12-tungstophosphoric acid (WPA) on conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) in the presence of Na + /K +-ATPase was monitored by 31 P NMR spectroscopy. It was shown that WPA exhibits inhibitory effect on Na + /K +-ATPase activity. In order to study WPA reactivity and inter-molecular interactions between WPA oxygen atoms and different proton donor types (D = O, N, C), we have considered data for WPA based compounds from the Cambridge Structural Database (CSD), the Crystallographic Open Database (COD) and the Inorganic Crystal Structure Database (ICSD). Binding properties of Keggin's anion in biological systems are illustrated using Protein Data Bank (PDB). This work constitutes the first determination of theoretical Bader charges on polyoxotungstate compound via the Atom In Molecule theory. An analysis of electrostatic potential maps at the molecular surface and charge of WPA, resulting from DFT calculations, suggests that the preferred protonation site corresponds to WPA bridging oxygen. These results enlightened WPA chemical reactivity and its potential biological applications such as the inhibition of the ATPase activity.

In this paper, we propose a simple cluster model with limited basis sets to reproduce the unpaired electron distributions in a YTiO

International audience; The paper describes a joint refinement model of the spin-resolved one-electron reduced density matrix using simultaneously magnetic structure factors and magnetic directional Compton profiles. The model is guided by two strategies: (i) variation of basis functions and (ii) variation of the spin population matrix. The implementation for a finite system is based on an expansion of the natural orbitals on basis sets. To show the potential benefits brought by the joint refinement model, the paper also presents the refinement results using magnetic structure factors only. The joint refinement model provides very satisfactory results reproducing the pseudo-data. In particular, magnetic Compton profiles have a strong effect not only on the off-diagonal elements of the spin-resolved one-electron reduced density matrix but also on its diagonal elements.

International audience; Joint refinement of X-ray and polarized neutron diffraction data has been carried out in order to determine charge and spin density distributions simultaneously in the nitro­nyl nitroxide (NN) free radical Nit(SMe)Ph. For comparison purposes, density functional theory (DFT) and complete active-space self-consistent field (CASSCF) theoretical calculations were also performed. Experimentally derived charge and spin densities show significant differences between the two NO groups of the NN function that are not observed from DFT theoretical calculations. On the contrary, CASSCF calculations exhibit the same fine details as observed in spin-resolved joint refinement and a clear asymmetry between the two NO groups.

Influence of 12-tungstophosphoric acid (WPA) on conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) in the presence of Na