Shape-restrained modelling of protein-small molecule complexes with HADDOCK

Small molecule docking remains one of the most valuable computational techniques for the structure prediction of protein-small molecule complexes. It allows us to study the interactions between compounds and the protein receptors they target at atomic detail, in a timely and efficient manner. Here we present a new protocol in HADDOCK, our integrative modelling platform, which incorporates homology information for both receptor and compounds. It makes use of HADDOCK's unique ability to integrate information in the simulation to drive it toward conformations which agree with the provided data. The focal point is the use of shape restraints derived from homologous compounds bound to the target receptors. We have developed two protocols: In the first, the shape is composed of fake atom beads based on the position of the heavy atoms of the homologous template compound, whereas in the second the shape is additionally annotated with pharmacophore data, for some or all beads. For both protocols, ambiguous distance restraints are subsequently defined between those beads and the heavy atoms of the ligand to be docked. We have benchmarked the performance of these protocols with a fully unbound version of the widely used DUD-E dataset. In this unbound docking scenario, our template/shape-based docking protocol reaches an overall success rate of 81% on 99 complexes, which is close to the best results reported for bound docking on the DUD-E dataset.

Low-temperature transport properties of n-type layered homologous compounds Bi8−xSbxSe7

The n-type chalcogenide Bi8Se7 is the parent compound of a new class of highly-efficient thermoelectric materials for near-room-temperature thermoelectric applications.

Rapid Visualization of Chemically Related Compounds Using Kendrick Mass Defect as a Filter in Mass Spectrometry Imaging

<div> <p>Kendrick mass defect (KMD) analysis is widely used for helping the detection and identification of chemically related compounds based on exact mass measurements. We report here the use of KMD as a criterion for filtering complex mass spectrometry dataset. The method enables an automated, easy and efficient data processing, enabling the reconstruction of 2D distributions of family of homologous compounds from MSI images. We show that the KMD filtering, based on an in-house software, is suitable and robust for high resolution (full width at half-maximum, FWHM, at <i>m/z</i> 410 of 20 000) and very high-resolution (FWHM, at <i>m/z</i> 410 of 160 000) MSI data. This method has been successfully applied to two different types of samples, bacteria co-cultures and brain tissue section</p> </div>

Rapid Visualization of Chemically Related Compounds Using Kendrick Mass Defect as a Filter in Mass Spectrometry Imaging

<div> <p>Kendrick mass defect (KMD) analysis is widely used for helping the detection and identification of chemically related compounds based on exact mass measurements. We report here the use of KMD as a criterion for filtering complex mass spectrometry dataset. The method enables an automated, easy and efficient data processing, enabling the reconstruction of 2D distributions of family of homologous compounds from MSI images. We show that the KMD filtering, based on an in-house software, is suitable and robust for high resolution (full width at half-maximum, FWHM, at <i>m/z</i> 410 of 20 000) and very high-resolution (FWHM, at <i>m/z</i> 410 of 160 000) MSI data. This method has been successfully applied to two different types of samples, bacteria co-cultures and brain tissue section</p> </div>

Preparation and molecular structures of N′-(2-heteroarylmethylidene)-3-(3-pyridyl)acrylohydrazides

The crystal and molecular structures of N′-(2-furylmethylidene)-3-(3-pyridyl)acrylohydrazide and N′-(2-thienylmethylidene)-3-(3-pyridyl)acrylohydrazide are reported, and the influence of the type of the heteroatom on the aromaticity of the aromatic rings is discussed. Both molecules are nearly planar. The geometry of the acrylohydrazide arrangement is comparable to that of homologous compounds. Density functional theory (DFT) calculations were performed in order to analyze the changes in the geometry of the studied compounds in the crystalline state and for the isolated molecule. The most significant changes were observed in the values of the N–N and C–N bond lengths. The harmonic oscillator model of aromaticity index, calculated for the furan and thiophene rings, demonstrated a noticeable increase in aromaticity in comparison to isolated rings and their DFT-calculated structures. By contrast, the nucleus independent chemical shift index indicated a decrease in aromatic character of the rings containing heteroatoms.

Triclinic conformational polymorph of N,N,N′,N′-tetrakis(2-cyanoethyl)-1,2-ethylenediamine (TCED)

The crystal and molecular structures of two polymorphs of N,N,N′,N′-tetrakis(2-cyanoethyl)-1,2-ethylenediamine have been characterized by X-ray diffraction along with density functional theory (DFT) studies. The molecules differ from each other by conformation. N,N,N′,N′-tetrakis(2-cyanoethyl)-1,2-ethylenediamine has been synthesized by cyanoethylation of ethylenediamine. Cyanoethylation of vicinal diamines is important for the synthesis of hyperbranched polymeric materials applied as catalysts, surfactants and encapsulating agents in drug delivery systems. The molecular geometry of N,N,N′,N′-tetracyanoethyl-1,2-ethylenediamine is similar to that of homologous compounds. DFT calculations were performed to analyze the differences in the molecular geometry of the studied compounds in a crystalline state and for an isolated molecule.