On the application of an experimental multipolar pseudo-atom library for accurate refinement of small-molecule and protein crystal structures

Zarychta, Bartosz; Pichon‐Pesme, Virginie; Guillot, Benoı̂t; Lecomte, Claude; Jelsch, Christian

doi:10.1107/s0108767306053748

Cited by 158 publications

(153 citation statements)

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“…the C atom in alanine) are nearly the same in all compounds containing this atom (Pichon-Pesme et al, 1995). Based on this principle, several databases of transferable multipole parameters have been developed (PichonPesme et al, 1995(PichonPesme et al, , 2004Volkov et al, 2004;Dittrich et al, 2006;Zarychta et al, 2007;Dominiak et al, 2007Dominiak et al, , 2009Domagała et al, 2012). They offer the possibility of constructing a multipole model of any molecule without the need to refine parameters beyond those of the IAM, i.e.…”

Section: Introductionmentioning

confidence: 99%

The active site of hen egg-white lysozyme: flexibility and chemical bonding

Held¹,

Smaalen²

2014

Acta Crystallogr D Biol Crystallogr

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Chemical bonding at the active site of hen egg-white lysozyme (HEWL) is analyzed on the basis of Bader's quantum theory of atoms in molecules [QTAIM;Bader (1994), Atoms in Molecules: A Quantum Theory. Oxford University Press] applied to electron-density maps derived from a multipole model. The observation is made that the atomic displacement parameters (ADPs) of HEWL at a temperature of 100 K are larger than ADPs in crystals of small biological molecules at 298 K. This feature shows that the ADPs in the cold crystals of HEWL reflect frozen-in disorder rather than thermal vibrations of the atoms. Directly generalizing the results of multipole studies on small-molecule crystals, the important consequence for electron-density analysis of protein crystals is that multipole parameters cannot be independently varied in a meaningful way in structure refinements. Instead, a multipole model for HEWL has been developed by refinement of atomic coordinates and ADPs against the X-ray diffraction data of Wang and coworkers [Wang et al. (2007), Acta Cryst. D63, 1254-1268], while multipole parameters were fixed to the values for transferable multipole parameters from the ELMAM2 database [Domagala et al. (2012), Acta Cryst. A68, 337-351] . Static and dynamic electron densities based on this multipole model are presented. Analysis of their topological properties according to the QTAIM shows that the covalent bonds possess similar properties to the covalent bonds of small molecules. Hydrogen bonds of intermediate strength are identified for the Glu35 and Asp52 residues, which are considered to be essential parts of the active site of HEWL. Furthermore, a series of weak C-HÁ Á ÁO hydrogen bonds are identified by means of the existence of bond critical points (BCPs) in the multipole electron density. It is proposed that these weak interactions might be important for defining the tertiary structure and activity of HEWL. The deprotonated state of Glu35 prevents a distinction between the Phillips and Koshland mechanisms.

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Section: Introductionmentioning

confidence: 99%

The active site of hen egg-white lysozyme: flexibility and chemical bonding

Held¹,

Smaalen²

2014

Acta Crystallogr D Biol Crystallogr

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“…This particular problem calls for special methods that couple restraints with nonlinear optimization. For example, methods that combine ab initio quantum-mechanical optimization with crystallographic refinement are being developed, and such methods need to be mentioned (Yu et al, 2005;Zarychta et al, 2007;Volkov et al, 2007).…”

mentioning

confidence: 99%

Comment onStereochemical restraints revisited: how accurate are refinement targets and how much should protein structures be allowed to deviate from them?by Jaskolski, Gilski, Dauter & Wlodawer (2007)

Stec

2007

Acta Crystallogr D Biol Cryst

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“…[45] The multipolar 1(r) model was expanded up to the dipolar order (l = 1) for the H atoms and up to the octupolar order (l = 3) for the C and N atoms, applying the corresponding geometrical constrains using the pro-gram MOPRO. [35,36,46] Optimization of the used restrains based on free R factors [47] was performed. CCDC 1062475 and 1062476 contain the supplementary crystallographic data for this paper.…”

Section: Methodsmentioning

confidence: 99%

“…[35,36,46] Optimization of the used restrains based on free R factors [47] was performed. CCDC 1062475 and 1062476 contain the supplementary crystallographic data for this paper.…”

Section: Methodsmentioning

confidence: 99%

Nature of Noncovalent Carbon‐Bonding Interactions Derived from Experimental Charge‐Density Analysis

2015

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In an effort to better understand the nature of noncovalent carbon-bonding interactions, we undertook accurate high-res-olution X-ray diffraction analysis of single crystals of 1,1,2,2-tetracyanocyclopropane. We selected this compound to study the fundamental characteristics of carbon-bonding interactions, because it provides accessible s holes. The study required extremely accurate experimental diffraction data, because the in-teraction of interest is weak. The electron-density distribution around the carbon nuclei, as shown by the experimental maps of the electrophilic bowl defined by a (CN)2C-C(CN)2 unit, was assigned as the origin of the interaction. This fact was also evidenced by plotting the D21(r) distribution. Taken together, the obtained results clearly indicate that noncovalent carbon bonding can be explained as an interaction between confront-ed oppositely polarized regions. The interaction is, thus elec-trophilic-nucleophilic (electrostatic) in nature and unambigu-ously considered as attractive.Attractive intermolecular electrostatic interactions encompass electron-rich and electron-poor regions of two molecules that complement each other.[1] Electron-rich entities are typically anions or lone-pair electrons and the most well-known elec-tron-poor entity is the hydrogen atom. Consequently, hydro-gen bonding is undoubtedly the most exploited supramolec-ular interaction.[2] Nowadays, another common electron-poor entity is attracting increasing attention in the literature. It is the 's hole', which can be defined as an electron-deficient anti-bonding orbital of a covalent bond. [3-13] Such regions of posi-tive electrostatic potential have been largely studied for atoms of groups V, VI, and VII (pnicogen, [14,15] chalcogen, [16][17][18] and hal-ogen [19-22] bonding, respectively [23] ) . Many reviews have described halogen bonding in detail, which is the best-known s-hole interaction. [6,[19][20][21][22] More recently, s-hole complexes with atoms of group IV, the tetrel (Tr) atoms, have been described, [24][25][26][27][28][29] and mostly focus on the heavier Tr atoms as tetrel-bond donors, leaving noncovalent carbon bonding much less studied. [30][31][32] In an sp 3 -hybridized electron-deficient C atom, there is only limited space available for an electron-rich guest molecule to nest itself. [31,32] To exem-plify this, we have represented in Figure 1 (right) the MEP sur- Figure 1.face of 1,1,2,2-tetracyanoethane (staggered conformation). The s hole is small and it is surrounded by negative belts, which hinder interactions with any concentration of negative charge (lone pair or anion). However, if the MEP surface is computed in the eclipsed conformation (C2v), the resulting s hole is more exposed and the electrostatic potential is considerable more positive. As a matter of fact, it has been recently demonstrated that the (CN) 2 C-C(CN) 2 motif of 1,1,2,2-tetracyanocyclopropane is an excellent carbon-bond donor, because the s hole is very exposed.[33] Moreover, it is synthetically accessible and the N_ C...

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On the application of an experimental multipolar pseudo-atom library for accurate refinement of small-molecule and protein crystal structures

Cited by 158 publications

References 48 publications

The active site of hen egg-white lysozyme: flexibility and chemical bonding

The active site of hen egg-white lysozyme: flexibility and chemical bonding

Comment onStereochemical restraints revisited: how accurate are refinement targets and how much should protein structures be allowed to deviate from them?by Jaskolski, Gilski, Dauter & Wlodawer (2007)

Nature of Noncovalent Carbon‐Bonding Interactions Derived from Experimental Charge‐Density Analysis

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