Modelling Electrostatic Potential from Experimentally Determined Charge Densities. II. Total Potential

Bouhmaida, Nouzha; Ghermani, Nour‐Eddine; Lecomte, Claude; Thalal, Abdelmalek

doi:10.1107/s0108767397004236

Cited by 37 publications

(30 citation statements)

References 11 publications

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“…An important longer-range aim of our studies is to determine experimental electrostatic parameters for biological macromolecules and to calibrate the theoretically derived electrostatic parameters used in biomolecular modeling calculations (31). Net atomic charges can, for instance, be derived experimentally from x-ray diffraction data via pseudoatom modeling (3,27,31). In analyses of small-molecule structures, spherical-atom charges refitted after multipolar refinements have been shown to yield molecular electric moments that agree well with independently measured experimental values (3,27).…”

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confidence: 83%

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confidence: 99%

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Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin

Jelsch

Teeter

Lamzin

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

213

171

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The charge density distribution of a protein has been refined experimentally. Diffraction data for a crambin crystal were measured to ultra-high resolution (0.54 Å) at low temperature by using shortwavelength synchrotron radiation. The crystal structure was refined with a model for charged, nonspherical, multipolar atoms to accurately describe the molecular electron density distribution. The refined parameters agree within 25% with our transferable electron density library derived from accurate single crystal diffraction analyses of several amino acids and small peptides. The resulting electron density maps of redistributed valence electrons (deformation maps) compare quantitatively well with a high-level quantum mechanical calculation performed on a monopeptide. This study provides validation for experimentally derived parameters and a window into charge density analysis of biological macromolecules.T he electronic charge density distribution of a molecule carries information (1) that determines its intermolecular interactions. For example, the charge distribution of an enzyme complements that of the substrate it recognizes and binds. The electrostatic potential and electric moments derivable from the charge density (1-3) provide maps that can guide the design of molecules for specified interactions. Furthermore, powerful insights into the nature and strength of hydrogen bonding and ionic interactions result from analysis of the electron density gradient and Laplacian (4-6). Extension of such analyses to proteins would permit a unique understanding of the driving forces between biomolecules as well as the subtleties of enzymatic reactions (7).Experimental electron density distributions are obtained by analysis of single-crystal x-ray diffraction data measured to ultra-high resolution, typically to a diffraction resolution limit d min Ϸ 0.5 Å (1,8,9). The crystallographic studies usually map and analyze the deformation density, which is the difference between the actual electron density of the molecule and the density calculated for the promolecule, a molecular superposition of spherical, neutral, i.e., free, atoms. The deformation density thus reveals the redistribution of valence electron density caused by chemical bonding and intermolecular interactions and also is used to calibrate theoretical electron density calculations (10). However, a difficulty in crystallography is the separation of the anisotropic atomic mean-square displacements from the static molecular electron distribution (11). Proper experimental deconvolution requires very accurate diffraction data to ultrahigh resolution. Thus, charge density studies have so far been limited to small-unit-cell crystals, and proteins still await study.We have shown (12, 13) that effective thermal displacement deconvolution and meaningful deformation density distributions can be achieved for larger structures at lower resolution by transferring average experimental electron density parameters. We have built a database of such parameters derived from ultra-high ...

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confidence: 83%

mentioning

confidence: 99%

Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin

Jelsch

Teeter

Lamzin

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

213

171

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“…The electrostatic potential of the isolated molecule has been computed using the program ELECTROS (Bouhmaida et al, 1997;Ghermani et al, 1993). The electrostatic potential È corresponding to the molecular charge-density distribution is given by the integrated form of the Poisson equation…”

Section: Electrostatic Potentialmentioning

confidence: 99%

Transferability of Multipole Charge-Density Parameters: Application to Very High Resolution Oligopeptide and Protein Structures

Jelsch

Pichon‐Pesme

Lecomte

et al. 1998

Acta Crystallogr D Biol Crystallogr

125

131

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Crystallography at sub-atomic resolution permits the observation and measurement of the non-spherical character of the electron density (parameterized as multipoles) and of the atomic charges. This ®ne description of the electron density can be extended to structures of lower resolution by applying the notion of transferability of the charge and multipole parameters. A database of such parameters has been built from charge-density analysis of several peptide crystals. The aim of this study is to assess for which X-ray structures the application of transferability is physically meaningful. The charge-density multipole parameters have been transferred and the X-ray structure of a 3 10 helix octapeptide Ac-Aib 2 -l-Lys(Bz)-Aib 2 -l-Lys(Bz)-Aib 2 -NHMe re®ned subsequently, for which diffraction data have been collected to a resolution of 0.82 A Ê at a cryogenic temperature of 100 K. The multipoles transfer resulted in a signi®cant improvement of the crystallographic residual factors wR and wR free. The accumulation of electrons in the covalent bonds and oxygen lone pairs is clearly visible in the deformation electron-density maps at its expected value. The re®nement of the charges for nine different atom types led to an additional improvement of the R factor and the re®ned charges are in good agreement with those of the AMBER molecular modelling dictionary. The use of scattering factors calculated from average results of charge-density work gives a negligible shift of the atomic coordinates in the octapeptide but induces a signi®cant change in the temperature factors (ÁB 9 0.4 A Ê 2 ). Under the spherical atom approximation, the temperature factors are biased as they partly model the deformation electron density. The transfer of the multipoles thus improves the physical meaning of the thermal-displacement parameters. The contribution to the diffraction of the different components of the electron density has also been analyzed. This analysis indicates that the electrondensity peaks are well de®ned in the dynamic deformation maps when the thermal motion of the atoms is moderate (B typically lower than 4 A Ê 2 ). In this case, a non-truncated Fourier synthesis of the deformation density requires that the diffraction data are available to a resolution better than 0.9 A Ê .

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“…where each atom j is at position R j in the crystal lattice, Z j being its nuclear positive charge (Ghermani et al, 1992a,b,c;Bouhmaida et al, 1997). In (2) N is the total number of atoms in the chemical system or molecule under consideration.…”

Section: Electrostatic Potential Field and Interaction Energymentioning

confidence: 99%

Charge density and electrostatic potential analyses in paracetamol

Bouhmaida

Bonhomme

Guillot

et al. 2009

Acta Crystallogr Sect B

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The electron density of monoclinic paracetamol was derived from high-resolution X-ray diffraction at 100 K. The HansenCoppens multipole model was used to refine the experimental electron density. The topologies of the electron density and the electrostatic potential were carefully analyzed. Numerical and analytical procedures were used to derive the charges integrated over the atomic basins. The highest charge magnitude (À1.2 e) was found for the N atom of the paracetamol molecule, which is in agreement with the observed nucleophilic attack occurring in the biological media. The electric field generated by the paracetamol molecule was used to calculate the atomic charges using the divergence theorem. This was simultaneously applied to estimate the total electrostatic force exerted on each atom of the molecule by using the Maxwell stress tensor. The interaction electrostatic energy of dimers of paracetamol in the crystal lattice was also estimated.

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Modelling Electrostatic Potential from Experimentally Determined Charge Densities. II. Total Potential

Cited by 37 publications

References 11 publications

Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin

Accurate protein crystallography at ultra-high resolution: Valence electron distribution in crambin

Transferability of Multipole Charge-Density Parameters: Application to Very High Resolution Oligopeptide and Protein Structures

Charge density and electrostatic potential analyses in paracetamol

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