Applying the charge density science methods to the structural biology field remains a considerable challenge. Several approaches were followed in the past years, focusing either on multipolar refinement of the rare available subatomic resolution protein structures or on the application of the transferability principle for the evaluation of electrostatic and energetic properties in protein-ligand complexes. However, the usually large size of macromolecules and the consequently large number of multipolar parameters in the Hansen & Coppens formalism [1] obviously complicates the feasibility of such kind of studies. In this presentation, we introduce the tools implemented in the MoProViewer software, part of the MoPro Suite for charge density refinement, especially designed to ease the analysis of a protein structure from a charge density perspective. These tools focus on helping the user in the computation of properties deriving from a refined or transferred [2] protein charge distribution and to manage a large number of atoms described in the multipole formalism in terms for instance of atomic local axis, symmetry or chemical equivalences constraints definitions. Moreover we will present new methods based on the topological analysis of the electrostatic potential [3]. They are designed to allow an original use of the electrostatic properties of a protein-ligand complex structure and rely on the computation and the representation of electrophilic and nucleophilic influence zones of atoms involved in protein-ligand interactions or in a biochemical process. The computational details of these methods as well as application examples on selected protein-ligand complexes will be given.

The new crystal structure of 2-carboxy-4-methylanilinium chloride monohydrate was determined by X-ray diffraction and refined using three different electrondensity models. In the first model, the ELMAM2 multipolar electron-density database was transferred to the molecule. Theoretical structure factors were also computed from periodic density functional theory calculations and yielded, after multipolar-atoms refinement, the second charge-density model. An alternative electron-density modelling, based on spherical atoms and additional charges on the covalent bonds and electron lone-pair sites, was used in the third model in the refinement versus the theoretical data. The crystallographic refinements, structural properties, electron-density distributions and molecular electrostatic potentials obtained from the different charge-density models were compared. As the number of variables refined in the different models is the same, the R factor is a good indicator of refinement quality. The R factor is best for multipolar modelling, presumably because of the greater flexibility and larger number of parameters to model the electron density compared to the sphericalcharges model. The electrostatic potentials around the molecule show a high correlation coefficient between the three models. research papers 454 Noureddine Dadda et al. Charge-density analysis using different models

Neutron and high-resolution X-ray crystallography were used to determine fully the structure of the internal water cluster in H-FABP. Analysis of the orientation and electrostatic properties of the water molecules showed significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field.

Errors on molecular properties including the topology of electron density and electrostatics are estimated from a sample of deviating models generated using the variance–covariance matrix issued at the end of the charge-density refinement.

Charge density studies on a few octahedrally coordinated Fe(II) complexes will be presented. The spin state of Fe(II) exhibits either high spin (HS) or low spin (LS) depending upon the ligand field strength of the coordinated ligands. Electron density distribution around the metal should be greatly different for the two spin states, namely a quintet 5 T 2 and a singlet 1 A 1 states. In order to eliminate any possible experimental differences, we choose a few systems where a HS and a LS state coexist in the same lattice. The comparison of these two spin states are quite clear, it gives a good example for the illustration of the d-orbital distributions of the 3d-transition metal as well as the metal-ligand bond for HS and LS state respectively in Fe(II) complexes. Complimentary x-ray absorption spectroscopy and the IR stretching frequency are also measured to monitor the spin transition. A DFT calculation is studied on one of the isolated molecules, comparable electron density distribution as well as the topological properties associated with the bond critical point with respect to the experimental observations will be discussed. The analysis of chemical bonding in real space can be performed using different position dependent functionals. Recently proposed Electron Localizability Indicator (ELI) is based on integrals over specially designed micro-cells [1]. Loosely speaking, ELI is proportional to the charge that is needed to form a same-spin electron pair. Thus, ELI is connected with the correlation of electronic motion of same-spin electrons [2]. In regions of space, where the bonding occurs, the same-spin electron try to avoid each other. The examination of metal-ligand bonds is complicated by the participation of the inner shell metal orbitals [3]. Some strategies, how to approach this difficult task will be presented. MS10 O2 Metal-ligand bonds in coordination compounds[1] Kohout M., Int. J. Quantum Chem., 2004, 97, 651. [2] Kohout M., Pernal K., Wagner F.R., Grin, Yu., Theor. Chem. Acc. 2004, 112, 453. [3] Kohout M., Wagner F.R., Grin, Yu., Theor. Chem. Acc. 2002, 108, 150. . Experimental deformation densities allow a first qualitative view of the non-spherical density and reveal fine details, coherent with the chemistry of the molecule, as for instance lack of electron density in the C-F bond [4][5][6], and larger density accumulation on imidazole moiety C-N and C-O bonds. The topological analysis of the total electron density performed using the VMoPro program [7] will be discussed. As the electrostatic properties are of major importance in numerous biological processes, accurate electrostatic potential and interaction energies calculations of the human aldose reductase complex with fidarestat will also be discussed. This will enable to give useful insight on the specific inhibition activity. Phys. Chem. B. 108,[3663][3664][3665][3666][3667][3668][3669][3670][3671][3672] [7] Jelsch, C., Guillot, B., Lagoutte, A. & Lecomte, C. (2005 The nature of the metal-metal bond in polynuclear transition me...