Structural Insights Into the 5′UG/3′GU Wobble Tandem in Complex With Ba2+ Cation

G•U wobble base pair frequently occurs in RNA structures. The unique chemical, thermodynamic, and structural properties of the G•U pair are widely exploited in RNA biology. In several RNA molecules, the G•U pair plays key roles in folding, ribozyme catalysis, and interactions with proteins. G•U may occur as a single pair or in tandem motifs with different geometries, electrostatics, and thermodynamics, further extending its biological functions. The metal binding affinity, which is essential for RNA folding, catalysis, and other interactions, differs with respect to the tandem motif type due to the different electrostatic potentials of the major grooves. In this work, we present the crystal structure of an RNA 8-mer duplex r[UCGUGCGA]2, providing detailed structural insights into the tandem motif I (5′UG/3′GU) complexed with Ba2+ cation. We compare the electrostatic potential of the presented motif I major groove with previously published structures of tandem motifs I, II (5′GU/3′UG), and III (5′GG/3′UU). A local patch of a strongly negative electrostatic potential in the major groove of the presented structure forms the metal binding site with the contributions of three oxygen atoms from the tandem. These results give us a better understanding of the G•U tandem motif I as a divalent metal binder, a feature essential for RNA functions.

Synthesis, Spectral Study and Theoretical Treatment of 2-(2-(4-bromocyclohexa-1, 3-dienyl)-4-oxo-2H- benz [1, 3] oxazin-3(4H)-ylamino)-2-oxoethyl carbamimidothioate and Derivatives.

The standard heat of formation (ΔHof) and binding energy (ΔEb) for the free compound and their derivatives are calculated by using the PM3 method at 273K of Hyperchem.-8.07 program. The compound is more stable than their derivatives. furthermore to investigate the reactive site of the molecules the electrostatic potential of free derivatives is measured and pm3 is used to evaluate the vibrational spectra of the free derivatives, the frequencies are obtained approximately agreed with those values experimentally found; in addition, the calculation helps to assign clearly the most diagnostic bands .

Semiempirical Quantum Chemical and Ab Intio Study of Co(Ii), Ni(Ii),Cu(Ii) and Zn(Ii) Complexes with the Azo Dye Derived from 4-Amino Antipyrine and 2,4-Dihydroxy Acetopheone

Semi-empirical quantum chemical calculation was made to study the nucleophilicity of the ligand and to study the mode of bonding between the ligand and the metal ions. The natural atomic charge at different atomic sites of the ligand has been calculated along with the electrostatic potential map to predict the reactive sites for electrophilic and nucleophilic attack. The theoretical spectral data such as IR, NMR and electronic have been calculated and compared with the experimentally generated data.

Influence of the Greater Protein Environment on the Electrostatic Potential in Metalloenzyme Active Sites: the Case of Formate Dehydrogenase

The Mo/W containing metalloenzyme formate dehydrogenase (FDH) is an efficient and selective natural catalyst which reversibly converts CO2 to formate under ambient conditions. A greater understanding of the role of the protein environment in determining the local properties of the FDH active site would enable rational bioinspired catalyst design. In this study, we investigate the impact of the greater protein environment on the electrostatic potential (ESP) of the active site. To model the enzyme environment, we used a combination of long-timescale classical molecular dynamics (MD) and multiscale quantum-mechanical/molecular-mechanical (QM/MM) simulations. We leverage the charge shift analysis method to systematically construct QM regions and analyze the electronic environment of the active site by evaluating the degree of charge transfer between the core active site and the protein environment. The contribution of the terminal chalcogen ligand to the ESP of the metal center is substantial and dependent on the chalcogen identity, with ESPs less negative and similar for Se and S terminal chalcogens than for O regardless of whether the Mo6+ or W6+ metal center is present. Our evaluation reveals that the orientation of the sidechains and ligand conformations will alter the relative trends in the ESP observed for a given metal center or terminal chalcogen, highlighting the importance of sampling dynamic fluctuations in the protein. Overall, our observations suggest that the terminal chalcogen ligand identity plays an important role in the enzymatic activity of FDH.

Reaction Mechanism About Isomerization of Resin Acids and Synthesis of Acrylopimaric Acid Based on DFT Calculation

Acrylopimaric acid is considered one of the possible substitutes for petroleum-based polymeric monomers, which is an important industrial product. Resin acids were isomerized to form levopimaric acid(4), which reacted with acrylic acid to synthesize isomers of acrylopimaric acid. Density functional theory calculation was used to investigate the reaction mechanisms with seven reaction paths in five different solutions. The values of ΔG were sorted from highest to lowest by levopimaric acid(4), neoabietic acid(3), palustric acid(2), and bietic acid(1). From the perspective of dynamics, the energy barrier in the isomerization of palustric acid(2) to levopimaric acid(4) was the lowest, whereas the highest energy barrier was the isomerization of neoabietic acid(3) to levopimaric acid(4) in the same solution. The addition reaction of levopimaric acid(4) and acrylic acid(5) to acrylopimaric acid c(8) was the optimal reaction path dynamically. However, ΔG of acrylopimaric acid c(8) was higher than that of acrylopimaric acid d(9). In general, the rates of isomerization reactions for rosin resin acids and addition reaction for acrylopimaric acid in water were higher than those in other solvents. HOMO-LUMO and ESP were analyzed for 8 kinds of molecules. For acylpyimaric acid, the non-planar six-memed ring and the C-C double bonds were easily attacked by nucleophile, while the non-planar six-memed ring and the carboxyl group are easily reacted with electrophiles. The highest electrostatic potential of the eight molecules is located at H of the carboxyl group, while the highest electrostatic potential is located at C-O double bond of the carboxyl group.

Omicron: A heavily mutated SARS-CoV-2 variant exhibits stronger binding to ACE2 and potently escape approved COVID-19 therapeutic antibodies

The new SARS-CoV-2 variant of concern “Omicron” was recently (Nov. 24th. 2021) spotted in South Africa and already spread around the world due to its enhanced transmissibility. The variant became conspicuous as it harbors more than thirty mutations in the spike protein with 15 mutations in the RBD region alone, potentially dampening the potency of therapeutic antibodies and enhancing the ACE2 binding. More worrying, Omicron infections have been reported in individuals who have received vaccines jabs in South Africa and Hong Kong. Here, we investigated the binding strength of Omicron with ACE2 and seven monoclonal antibodies that are either approved by FDA for COVID-19 therapy or undergoing phase III clinical trials. Computational mutagenesis and binding free energies could confirm that Omicron Spike binds ACE2 stronger than prototype SARS-CoV-2. Notably, three substitutions, i.e., T478K, Q493K, and Q498R, significantly contribute to the binding energies and doubled electrostatic potential of the RBDOmic-ACE2 complex. Instead of E484K substitution that helped neutralization escape of Beta, Gamma, and Mu variants, Omicron harbors E484A substitution. Together, T478K, Q493K, Q498R, and E484A substitutions contribute to a significant drop in the electrostatic potential energies between RBDOmic-mAbs, particularly in Etesevimab, Bamlanivimab, and CT-p59. CDR diversification could help regain the neutralization strength of these antibodies; however, we could not conduct this analysis to this end. Conclusively, our findings suggest that Omicron binds ACE2 with greater affinity, enhancing its infectivity and transmissibility. Mutations in the Spike are prudently devised by the virus that enhances the receptor binding and weakens the mAbs binding to escape the immune response.

The Cyclobutanocucurbit[5–8]uril Family: Electronegative Cavities in Contrast to Classical Cucurbituril while the Electropositive Outer Surface Acts as a Crystal Packing Driver

The structural parameters for the cyclobutanoQ[5–8] family were determined through single crystal X-ray diffraction. It was found that the electropositive cyclobutano methylene protons (CH2) are important in forming interlinking crystal packing arrangements driven by the dipole–dipole interactions between these protons and the portal carbonyl O of a near neighbor. This type of interaction was observed across the whole family. Electrostatic potential maps also confirmed the electropositive nature of the cyclobutano CH2 but, more importantly, it was established that the cavities are electronegative in contrast to classical Q[5–8], which are near neutral.

Substrate-induced electrostatic potential varies composition of supported lipid bilayer containing anionic lipid

Supported lipid bilayers (SLBs) are artificial lipid bilayers at solid-liquid interfaces applied as cell membrane model systems. An advantage of the artificial system is that the lipid composition can be controlled arbitrarily. On the other hand, the SLB formation process and its efficiency are affected by the properties of the solid substrate surface. In this study, we investigated the effect of the electrostatic interaction between the negatively charged SiO2/Si substrate surface and the lipid bilayer membrane on the composition of binary SLBs comprising anionic and neutral lipids. The phase transition temperature and the area fraction of lipid domains of SLB were evaluated by fluorescence microscopy and the fluorescence recovery after photobleaching. The neutral lipid was preferably included in SLB, but the anionic lipid ratio increased with Ca2+ concentration during the SLB formation. The lipid composition in SLB can be controlled by modulating the substrate-induced electrostatic potential.