Brassinosteroids Positively Modulate Growth: Physiological,Biochemical and Anatomical Evidence Using Two Tomato Genotypes Contrasting to Dwarfism

Growth and development are vital processes in the life cycles of plants. Brassinosteroids (BRs) are steroids that when exogenously applied can regulate several biological responses. The aim of this research was to investigate the possible interferences caused by the exogenous application of BR on growth and metabolism using two genotypes of the DWARF gene, MT-d and MT-D, that are BR-deficient and BR-efficient, respectively. The experiment had four treatments with two genotypes (BR-efficient and BR-deficient) and two levels of brassinosteroids (0 and 100 nM BR, described as ??BR and +?BR, respectively). This study revealed that the exogenous application of BR promoted improvement in growth, inducing increases in all variables of both genotypes evaluated. In general, BR-deficient plants sprayed with BR had effects more intense, confirming the benefits of this steroid on photosynthetic apparatus and gas exchange. The changes in the anatomical characteristics of the leaf are related to the contribution of BR on the influx and consequent fixation of CO₂. In addition, modifications related to root anatomy occurred as a result of the BR action with the purpose of increasing the root protection and absorption of water and nutrients. Increases in photosynthetic pigments suggest that the role of BR is linked with chlorophyll biosynthesis and the maintenance of chloroplast integrity, resulting from associations with the increases found in the activities of antioxidant enzymes that modulate the accumulation of reactive oxygen species.     

The neural γ<Subscript>2</Subscript>α<Subscript>1</Subscript>β<Subscript>2</Subscript>α<Subscript>1</Subscript>β<Subscript>2</Subscript> gamma amino butyric acid ion channel receptor: structural analysis of the effects of the ivermectin molecule and disulfide bridges

While ~30% of the human genome encodes membrane proteins, only a handful of structures of membrane proteins have been resolved to high resolution. Here, we studied the structure of a member of the Cys-loop ligand gated ion channel protein superfamily of receptors, human type A γ₂α₁β₂α₁β₂ gamma amino butyric acid receptor complex in a lipid bilayer environment. Studying the correlation between the structure and function of the gamma amino butyric acid receptor may enhance our understanding of the molecular basis of ion channel dysfunctions linked with epilepsy, ataxia, migraine, schizophrenia and other neurodegenerative diseases. The structure of human γ₂α₁β₂α₁β₂ has been modeled based on the X-ray structure of the Caenorhabditis elegans glutamate-gated chloride channel via homology modeling. The template provided the first inhibitory channel structure for the Cys-loop superfamily of ligand-gated ion channels. The only available template structure before this glutamate-gated chloride channel was a cation selective channel which had very low sequence identity with gamma aminobutyric acid receptor. Here, our aim was to study the effect of structural corrections originating from modeling on a more reliable template structure. The homology model was analyzed for structural properties via a 100 ns molecular dynamics (MD) study. Due to the structural shifts and the removal of an open channel potentiator molecule, ivermectin, from the template structure, helical packing changes were observed in the transmembrane segment. Namely removal of ivermectin molecule caused a closure around the Leu 9 position along the ion channel. In terms of the structural shifts, there are three potential disulfide bridges between the M1 and M3 helices of the γ₂ and 2 α₁ subunits in the model. The effect of these disulfide bridges was investigated via monitoring the differences in root mean square fluctuations (RMSF) of individual amino acids and principal component analysis of the MD trajectory of the two homology models—one with the disulfide bridge and one with protonated Cys residues. In all subunit types, RMSF of the transmembrane domain helices are reduced in the presence of disulfide bridges. Additionally, loop A, loop F and loop C fluctuations were affected in the extracellular domain. In cross-correlation analysis of the trajectory, the two model structures displayed different coupling in between the M2–M3 linker region, protruding from the membrane, and the β1-β2/D loop and cys-loop regions in the extracellular domain. Correlations of the C loop, which collapses directly over the bound ligand molecule, were also affected by differences in the packing of transmembrane helices. Finally, more localized correlations were observed in the transmembrane helices when disulfide bridges were present in the model. The differences observed in this study suggest that dynamic coupling at the interface of extracellular and ion channel domains differs from the coupling introduced by disulfide bridges in the transmembrane region. We hope that this hypothesis will be tested experimentally in the near future.     

Identification of small molecule inhibitors of ALK2: a virtual screening,density functional theory,and molecular dynamics simulations study

Bone morphogenetic proteins (BMPs) are a family of more than 30 ligands and several receptors, such as activin like kinases (ALKs) and bone morphogenetic protein receptor (BMPR). Physiological significance of these proteins lies in their prominent role during homeostasis, apoptosis, tissue remodeling, embryonic patterning, and normal development. Fibrodysplasia ossificans progressive (FOP) is one among several other diseases caused by impaired BMP signaling. FOP is caused by the pathogenicity of activating mutation of ALK2. In order to treat FOP, a search for good inhibitors of ALK2 based on dorsomorphin and LDN substitution, which in essence is a ligand based search of inhibitors, is in progress. Contributing to this area of research we identified several lead molecules based on protein structure using virtual screening. After virtual screening of a huge library of small molecules and ab initio calculation of selected molecules for drug efficacy, we did molecular dynamic simulation of lead molecules and protein complexes. We identified five potential drug molecules that show very stable binding on the same binding site as LDN-213844. We also ranked these lead molecules based on MM/PBSA binding energy. This study provides a basis to think beyond the pyrimidine nucleus of dorsomorphin/LDN and design new chemical derivatives for effective treatment of FOP.

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Graphical abstract Small molecule inhibitors of ALK2

     

Theoretical study of the NMR chemical shift of Xe in supercritical condition

In this work we investigate the level of theory necessary for reproducing the non-linear variation of the ¹²⁹Xe nuclear magnetic resonance (NMR) chemical shift with the density of Xe in supercritical conditions. In detail we study how the ¹²⁹Xe chemical shift depends under supercritical conditions on electron correlation, relativistic and many-body effects. The latter are included using a sequential-QM/MM methodology, in which a classical MD simulation is performed first and the chemical shift is then obtained as an average of quantum calculations of 250 MD snapshots conformations carried out for Xe _n clusters (n =?2 ? 8 depending on the density). The analysis of the relativistic effects is made at the level of 4-component Hartree-Fock calculations (4c-HF) and electron correlation effects are considered using second order Møller-Plesset perturbation theory (MP2). To simplify the calculations of the relativistic and electron correlation effects we adopted an additive scheme, where the calculations on the Xe _n clusters are carried out at the non-relativistic Hartree-Fock (HF) level, while electron correlation and relativistic corrections are added for all the pairs of Xe atoms in the clusters. Using this approach we obtain very good agreement with the experimental data, showing that the chemical shift of ¹²⁹Xe in supercritical conditions is very well described by cluster calculations at the HF level, with small contributions from relativistic and electron correlation effects.     

A computational investigation on the antioxidant potential of myricetin 3,4′-di-<Emphasis Type="Italic">O</Emphasis>-<Emphasis Type="Italic">α</Emphasis>-<Emphasis Type="Italic">L</Emphasis>-rhamnopyranoside

In this work, we present a computational study on the antioxidant potential of myricetin 3,4\(^{\prime }\)-di-O-α-L-rhamnopyranoside (Compound M). A density functional theory (DFT) approach with the B3LYP and LC-ωPBE functionals and with both the 6-311G(d,p) and 6-311+G(d,p) basis sets was used. The focus of the investigation was on the structural and energetic parameters including both bond dissociation enthalpies (BDEs) and ionization potentials (IPs), which provide information on the potential antioxidant activity. The properties computed were compared with BDEs and IPs available in the literature for myricetin, a compound well known for presenting antioxidant activity (and the parent molecule of the compound of interest in the present work). Myricetin 3,4\(^{\prime }\)-di-O-α-L-rhamnopyranoside presented the lowest BDE to be 79.13 kcal/mol (as determined using B3LYP/6-311G(d,p) in water) while myricetin has a quite similar value (within 3.4 kcal/mol). IPs computed in the gas phase [B3LYP/6-311G(d,p)] are 157.18 and 161.4 kcal/mol for myricetin 3,4\(^{\prime }\)-di-O-α-L-rhamnopyranoside and myricetin, respectively. As the values of BDEs are considerably lower than the ones probed for IPs (in the gas phase or in any given solvent environment), the hydrogen atom transfer mechanism is preferred over the single electron transfer mechanism. The BDEs obtained suggest that myricetin 3,4\(^{\prime }\)-di-O-α-L-rhamnopyranoside can present antioxidant potential as good as the parent molecule myricetin (a well-known antioxidant). Therefore, experimental tests on the antioxidant activity of Compound M are encouraged.     

Theoretical study on benzoheterocycle based energetic materials,effect of heterocyclic-fused,conjugation, hydrogen bond,and substitutional group on the detonation performance

In this paper, four series of benzoheterocycle based energetic materials (EMs) have been designed to plan out a strategy to improve the density and safety of EMs, such as combining the insensitive group with aminobenzene ring and the high energetic nitramine explosives, benzo-heterocycle mother ring, designing multi-nitrogen heterocycles with a conjugated system containing N-N and C-N high energy bonds, and hydrogen bonding. Their optimized structure and detonation properties were first calculated and discussed using DFT methods. After calculation, these designed explosives all showed good detonation from 7352 m/s to 8788 m/s. Among them, the compounds with six nitro groups, 1c, 2c, 3c, and 4c, exhibit better performance and rather poor impact sensitivity. However, we found that the compounds with five nitro groups and one amino group have a limited performance reduction and a rapid stability improvement. These four compounds, 1b, 2b, 3b, and 4b, have good detonation performance and better stability. Moreover, the synthesis routes for these four compounds were also designed. The precursor 4–0 and mononitro product 4–1 were successfully synthesized. Their 1H NMR, single crystal, and elemental analysis were also done to verify the structures.     

Microwave effects on NiMoS and CoMoS single-sheet catalysts

Single-sheet nanoclusters of MoS₂, NiMoS or CoMoS are widely used in hydrodesulfurization (HDS) catalysis in the petroleum industry. In HDS reactions under microwave irradiation, experiments indirectly pointed out that for pristine MoS₂ reaction rates are accelerated because hot spots are generated on the catalyst bed. In this work, we investigated NiMoS and CoMoS isolated single-sheet substituted catalysts before and after thiophene adsorption focusing on quantifying the effect of microwave irradiation. For that purpose, density functional theory (DFT) molecular charge densities of each system were decomposed according to the distributed multipole analysis (DMA) of Stone. Site dipole values of each system were directly associated with a larger or smaller interaction with the microwave field according to a proposed general approach. We showed that microwave enhancement of HDS reaction rates can occur more efficiently in the CoMoS and NiMoS promoted clusters compared to pristine MoS₂ in the following order: CoMoS > NiMoS > MoS₂. The atomic origin of the catalyst hot spots induced by microwaves was clearly established in the promoted clusters.     

Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments

Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.     

Conjugation in multi-tetrazole derivatives: a new design direction for energetic materials

Multi-tetrazole derivatives with conjugated structures were designed and investigated in this study. Using quantum chemistry methods, the crystal structures, electrostatic potentials (ESPs), multicenter bond orders, HOMO–LUMO energy gaps, and detonation properties of the derivatives were calculated. As expected, these molecules with conjugated structures showed low energies of their crystal structures, molecular layering in their crystals, high average ESPs, high multicenter bond order values, and enhanced detonation properties. The derivative 1,2-di(1H-tetrazol-5-yl)diazene (N2) was predicted to have the best density (1.87 g/cm³), detonation velocity (9006 m/s), and detonation pressure (36.8 GPa) of the designed molecules, while its total crystal energy was low, suggesting that it is relatively stable. Its sensitivity was also low, as the molecular stacking that occurs in its crystal allows external forces to be dissipated into movements of crystal layers. Finally, its multicenter bond order was high, indicating a highly conjugated structure.