Electron density based analysis of N–H⋯OC hydrogen bonds and electrostatic interaction energies in high-resolution secondary protein structures: insights from quantum crystallographic approaches

CrystEngComm ◽  
2020 ◽  
Vol 22 (26) ◽  
pp. 4363-4373 ◽  
Author(s):  
Suman K. Mandal ◽  
Benoît Guillot ◽  
Parthapratim Munshi
Keyword(s):  
High Resolution ◽  
Hydrogen Bonds ◽  
Electron Density ◽  
Electrostatic Interaction ◽  
Main Chain ◽  
Protein Structures ◽  
Interaction Energies ◽  
Topological Parameters ◽  
Limiting Values ◽  
Qualitative Analyses

Limiting values of the topological parameters and the electrostatic interaction energies to establish the presence of true N–H⋯OC H-bonds in protein main-chain have been identified using quantitative and qualitative analyses of electron densities.

Fast analytical evaluation of intermolecular electrostatic interaction energies using the pseudoatom representation of the electron density. III. Application to crystal structures via the Ewald and direct summation methods

2020 ◽  
Vol 76 (6) ◽  
pp. 630-651
Author(s):  
Daniel Nguyen ◽  
Piero Macchi ◽  
Anatoliy Volkov
Keyword(s):  
Interaction Energy ◽  
Crystal Structures ◽  
Electron Density ◽  
Small Molecule ◽  
Electrostatic Interaction ◽  
Multipole Moment ◽  
Interaction Energies ◽  
Acta Cryst ◽  
Löwdin Α Function ◽  
Direct Summation

The previously reported exact potential and multipole moment (EP/MM) method for fast and accurate evaluation of the intermolecular electrostatic interaction energies using the pseudoatom representation of the electron density [Volkov, Koritsanszky & Coppens (2004). Chem. Phys. Lett. 391, 170–175; Nguyen, Kisiel & Volkov (2018). Acta Cryst. A74, 524–536; Nguyen & Volkov (2019). Acta Cryst. A75, 448–464] is extended to the calculation of electrostatic interaction energies in molecular crystals using two newly developed implementations: (i) the Ewald summation (ES), which includes interactions up to the hexadecapolar level and the EP correction to account for short-range electron-density penetration effects, and (ii) the enhanced EP/MM-based direct summation (DS), which at sufficiently large intermolecular separations replaces the atomic multipole moment approximation to the electrostatic energy with that based on the molecular multipole moments. As in the previous study [Nguyen, Kisiel & Volkov (2018). Acta Cryst. A74, 524–536], the EP electron repulsion integral is evaluated analytically using the Löwdin α-function approach. The resulting techniques, incorporated in the XDPROP module of the software package XD2016, have been tested on several small-molecule crystal systems (benzene, L-dopa, paracetamol, amino acids etc.) and the crystal structure of a 181-atom decapeptide molecule (Z = 4) using electron densities constructed via the University at Buffalo Aspherical Pseudoatom Databank [Volkov, Li, Koritsanszky & Coppens (2004). J. Phys. Chem. A, 108, 4283–4300]. Using a 2015 2.8 GHz Intel Xeon E3-1505M v5 computer processor, a 64-bit implementation of the Löwdin α-function and one of the higher optimization levels in the GNU Fortran compiler, the ES method evaluates the electrostatic interaction energy with a numerical precision of at least 10−5 kJ mol−1 in under 6 s for any of the tested small-molecule crystal structures, and in 48.5 s for the decapeptide structure. The DS approach is competitive in terms of precision and speed with the ES technique only for crystal structures of small molecules that do not carry a large molecular dipole moment. The electron-density penetration effects, correctly accounted for by the two described methods, contribute 28–64% to the total electrostatic interaction energy in the examined systems, and thus cannot be neglected.

scholarly journals Toward a uniform description of hydrogen bonds and halogen bonds: correlations of interaction energies with various geometric, electronic and topological parameters

RSC Advances ◽  
2017 ◽  
Vol 7 (17) ◽  
pp. 10295-10305 ◽  
Author(s):  
Jian-Wei Zou ◽  
Meilan Huang ◽  
Gui-Xiang Hu ◽  
Yong-Jun Jiang
Keyword(s):  
Hydrogen Bonds ◽  
Structural Parameters ◽  
Interaction Energies ◽  
Halogen Bonds ◽  
Topological Parameters

Correlations between interaction energies and various structural parameters were established to reveal the differences between hydrogen bonds and halogen bonds.

scholarly journals Rapid model building of α-helices in electron-density maps

2010 ◽  
Vol 66 (3) ◽  
pp. 268-275 ◽  
Author(s):  
Thomas C. Terwilliger
Keyword(s):  
High Resolution ◽  
Electron Density ◽  
Model Building ◽  
Main Chain ◽  
Rapid Identification ◽  
Side Chains ◽  
Low Resolution ◽  
Density Maps ◽  
Experimental Electron Density

A method for the identification of α-helices in electron-density maps at low resolution followed by interpretation at moderate to high resolution is presented. Rapid identification is achieved at low resolution, where α-helices appear as tubes of density. The positioning and direction of the α-helices is obtained at moderate to high resolution, where the positions of side chains can be seen. The method was tested on a set of 42 experimental electron-density maps at resolutions ranging from 1.5 to 3.8 Å. An average of 63% of the α-helical residues in these proteins were built and an average of 76% of the residues built matched helical residues in the refined models of the proteins. The overall average r.m.s.d. between main-chain atoms in the modeled α-helices and the nearest atom with the same name in the refined models of the proteins was 1.3 Å.

scholarly journals New Ligands and New Insights for Vitamin D Receptor from Charge Density

2014 ◽  
Vol 70 (a1) ◽  
pp. C966-C966
Author(s):  
Maura Malińska ◽  
Andrzej Kutner ◽  
Krzysztof Woźniak
Keyword(s):  
Vitamin D ◽  
Hydrogen Bonds ◽  
Charge Density ◽  
Interaction Energy ◽  
Vitamin D Receptor ◽  
Electrostatic Interaction ◽  
Interaction Energies ◽  
Average Strength ◽  
Vitamin D Analogs ◽  
Wide Range

Vitamin D protective effects result from its role as a nuclear transcription factor that regulates cell growth, differentiation, and a wide range of cellular mechanisms crucial to the development and progression of cancer.[1] Many academic investigators and pharmaceutical companies try to develop calcitriol analogs that exhibit equal or even increased anti-proliferative activity while exhibiting a reduced tendency to cause hypercalcemia. Analysis of 24 Vitamin D analogs bearing similar molecular structures with a complex of a Vitamin D Receptor (VDR) enabled the design of new agonists (TB1, TB2, TB3 and TB4). Undertaken approach was to minimize the electrostatic interaction energies available after the reconstruction of charge density with the aid of the pseudoatom databank (UBDB[2]). Comprehensive studies revealed 29 residues crucial for agonist binding. Trp286, which is specific to VDR among the representatives of the Nuclear Receptor Family, plays the crucial role of positioning the ligand forming dispersive interactions, mostly C-H...π, with an average strength of -4 kcal mol-1. The ligand binding pocket is primarily composed of hydrophobic residues, however there are 6 hydrogen bonds characteristic for all the ligands. They electrostatic interaction energies strongly contribute to the total interaction energy, with an average strength of -8, -19, -11 and -12 kcal mol-1 for hydrogen bonds to Ser237, Arg274, Ser278 and Tyr143. The aliphatic chain of the Vitamin D analogs adopt an extended conformation and the 25-hydroxyl group is hydrogen bonded to His305 and His397 with electrostatic interaction energies of -13 and -11 kcal mol-1. The geometries of complexes of the proposed ligand with VDR were obtained by the docking procedure implemented in Autodock4.3[3]. New agonsits form all mentioned before interactions with VDR. The final results of electrostatic interaction energy for TB1 and TB2 are -153 and -120 kcal mol-1, and this results are the smallest among all studied Vitamin D analogs.

The whole range of hydrogen bonds in one crystal structure: neutron diffraction and charge-density studies of N,N-dimethylbiguanidinium bis(hydrogensquarate)

2011 ◽  
Vol 67 (6) ◽  
pp. 552-559 ◽  
Author(s):  
Mihaela-Diana Şerb ◽  
Ruimin Wang ◽  
Martin Meven ◽  
Ulli Englert
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
High Resolution ◽  
Hydrogen Bonds ◽  
Neutron Diffraction ◽  
Electron Density ◽  
Organic Salt ◽  
X Ray Diffraction ◽  
Covalent Character ◽  
X Ray

N,N-Dimethylbiguanidinium bis(hydrogensquarate) features an impressive range of hydrogen bonds within the same crystal structure: neighbouring anions aggregate to a dianionic pair through two strong O—H...O interactions; one of these can be classified among the shortest hydrogen bonds ever studied. Cations and anions in this organic salt further interact via conventional N—H...O and nonclassical C—H...O contacts to an extended structure. As all these interactions occur in the same sample, the title compound is particularly suitable to monitor even subtle trends in hydrogen bonds. Neutron and high-resolution X-ray diffraction experiments have enabled us to determine the electron density precisely and to address its properties with an emphasis on the nature of the X—H...O interactions. Sensitive criteria such as the Laplacian of the electron density and energy densities in the bond-critical points reveal the incipient covalent character of the shortest O—H...O bond. These findings are in agreement with the precise geometry from neutron diffraction: the shortest hydrogen bond is also significantly more symmetric than the longer interactions.

Kinematic Motion Constraints of the Protein Molecule Chains

2011 ◽  
Author(s):  
Zahra Shahbazi ◽  
Horea T. Ilies¸ ◽  
Kazem Kazerounian
Keyword(s):  
Hydrogen Bonds ◽  
Degrees Of Freedom ◽  
Main Chain ◽  
Protein Structures ◽  
Protein Molecule ◽  
Correct Identification ◽  
Closed Loops ◽  
Motion Constraints ◽  
Protein Molecules ◽  
Internal Mobility

The function of protein molecules is defined by their 3-D geometry, as well as their internal mobility, which is heavily influenced by the internal hydrogen bonds. The correct identification of these hydrogen bonds and the prediction of their effect on the mobility of protein molecules can provide an invaluable mechanism to understand protein behavior. Applications of this study ranges from nano-engineering to new drug design. We are extending our recent approach from identifying main-chain main-chain hydrogen bonds to all types of hydrogen bonds that occur in protein structures, such as α-helices and β-sheets. We use the Gru¨bler-Kutzbach kinematic mobility criterion to determine the degrees of freedom of all closed loops (rigid loops as well as closed loops of one or more degrees of freedom) formed by Hydrogen bonds. Furthermore, we systematically develop constraint equations for non-rigid closed loops. Several examples of protein molecules from PDB are used to show that these additions both improve the accuracy of mobility analysis and enable us to study a broader range of the motion of protein molecules. This approach offers theoretical insight as well as extensive numerical efficiencies in protein simulations.

How the oxazole fragment influences the conformation of the tetraoxazocane ring in a cyclohexanespiro-3′-(1,2,4,5,7-tetraoxazocane): single-crystal X-ray and theoretical study

2019 ◽  
Vol 75 (10) ◽  
pp. 1439-1447
Author(s):  
Leonard M. Khalilov ◽  
Ekaterina S. Mescheryakova ◽  
Kamil Sh. Bikmukhametov ◽  
Nataliya N. Makhmudiyarova ◽  
Kamil R. Shangaraev ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Electron Density ◽  
Topological Analysis ◽  
Chair Conformation ◽  
Considerable Effect ◽  
Intramolecular Interactions ◽  
X Ray ◽  
Topological Parameters ◽  
Dispersion Component ◽  
Hirshfeld Analysis

Single crystals of (2S,5R)-2-isopropyl-5-methyl-7-(5-methylisoxazol-3-yl)cyclohexanespiro-3′-(1,2,4,5,7-tetraoxazocane), C16H26N2O5, have been studied via X-ray diffraction. The tetraoxazocane ring adopts a boat–chair conformation in the crystalline state, which is due to intramolecular interactions. Conformational analysis of the tetraoxazocane fragment performed at the B3LYP/6-31G(d,2p) level of theory showed that there are three minima on the potential energy surface, one of which corresponds to the conformation realized in the solid state, but not to a global minimum. Analysis of the geometry and the topological parameters of the electron density at the (3,−1) bond critical points (BCPs), and the charge transfer in the tetraoxazocane ring indicated that there are stereoelectronic effects in the O—C—O and N—C—O fragments. There is a two-cross hyperconjugation in the N—C—O fragment between the lone electron pair of the N atom (lpN) and the antibonding orbital of a C—O bond (σ*C—O) and vice versa between lpO and σ*C—N. The oxazole substituent has a considerable effect on the geometry and the topological parameters of the electron density at the (3,−1) BCPs of the tetraoxazocane ring. The crystal structure is stabilized via intermolecular C—H...N and C—H...O hydrogen bonds, which is unambiguously confirmed with PIXEL calculations, a quantum theory of atoms in molecules (QTAIM) topological analysis of the electron density at the (3,−1) BCPs and a Hirshfeld analysis of the electrostatic potential. The molecules form zigzag chains in the crystal due to intermolecular C—H...N interactions being electrostatic in origin. The molecules are further stacked due to C—H...O hydrogen bonds. The dispersion component in the total stabilization energy of the crystal lattice is 68.09%.

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