Domain Mobility in the ORF2p Complex Revealed by Molecular Dynamics Simulations and Big Data Analysis.

ORF2p (open reading frame 2 protein) is a multifunctional multidomain enzyme that demonstrates both reverse transcriptase and endonuclease activities and is associated with the pathophysiology of cancer. The 3D structure of the entire seven-domain ORF2p complex was revealed with the recent achievements in structural studies. The different arrangements of the CTD (carboxy-terminal domain) and tower domains were identified as the "closed-ring" and "open-ring" conformations, which differed by the hairpin position of the tower domain, but the structural diversity of these complexes has the potential to be more extensive.

Error compensated MOF-based ReRAM array for encrypted logical operations.

Metal-organic frameworks (MOFs) form a unique platform for operation with data using ReRAM technology. Here we report on a large-scale fabrication of a MOF-based ReRAM array with 6 × 6 cells, demonstrating 50% variation in their electronic parameters. Despite this inhomogeneity, such a "non-ideal" ReRAM array is used for recording binary information followed by deep learning processes to achieve 95% accuracy of reading.

Molecular Basis of the Substrate Specificity of Phosphotriesterase from : A Combined QM/MM MD and Electron Density Study.

The occurrence of organophosphorus compounds, pesticides, and flame-retardants in wastes is an emerging ecological problem. Bacterial phosphotriesterases are capable of hydrolyzing some of them. We utilize modern molecular modeling tools to study the hydrolysis mechanism of organophosphorus compounds with good and poor leaving groups by phosphotriesterase from Pseudomonas diminuta (Pd-PTE).

Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.

Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F(CBA×C57BL/6) hybrid mice in a dose-dependent manner.

Luminescent Ln-based silsesquioxanes with a β-diketonate antenna ligand: toward the design of efficient temperature sensors.

We report the synthesis and single-crystal X-ray diffraction, magnetic, and luminescence measurements of a novel family of luminescent cage-like tetranuclear silsesquioxanes (PhSiO)(LnO)(O)(CHO)(EtOH)(CHCN)â‹…2CHCN (where Ln = Tb, ; Tb/Eu, ; and Gd, ), featuring seven-coordinated lanthanide ions arranged in a one-capped trigonal prism geometry. Compounds and exhibit characteristic Tb and Tb/Eu-related emissions, respectively, sensitized by the chelating antenna acetylacetonate (acac) ligands upon excitation in the UV and visible spectral regions. Compound is used to assess the energies of the triplet states of the ligand.

Potato Solanum tuberosum L. Phytoene Synthase Genes (StPSY1, StPSY2, and StPSY3) Are Involved in the Plant Response to Cold Stress.

The structure and phylogeny of the Solanum tuberosum L. phytoene synthase genes StPSY1, StPSY2, and StPSY3 were characterized. Their expression was studied in potato seedlings exposed to cold stress in the dark phase of the diurnal cycle to simulate night cooling.

Prediction of Metal-Organic Frameworks with Phase Transition via Machine Learning.

Metal-organic frameworks (MOFs) possess a virtually unlimited number of potential structures. Although the latter enables an efficient route to control the structure-related functional properties of MOFs, it still complicates the prediction and searching for an optimal structure for specific application. Next to prediction of the MOFs for gas sorption/separation and catalysis via machine learning (ML), we report on ML to find MOFs demonstrating a phase transition (PT).

Tetranuclear lanthanide-based silsesquioxanes: towards a combination of a slow relaxation of the magnetization and a luminescent thermometry.

Lanthanide-based silsesquioxanes constitute an emerging family of cage-like metallasilsesquioxanes with exciting optical and magnetic properties. We report here the synthesis, structures and luminescence properties of a series of tetranuclear lanthanide-silsesquioxane compounds of general formula [NEt][(PhSiO)(Ln/Ln')(NO)(EtOH)(MeCN)]·4(MeCN) with different lanthanide ions (where Ln/Ln' = Dy/Eu (1), Dy/Tb (2) and Eu/Tb/Y (3)) and investigate the impact of the lanthanide ions combination on magnetic and photo-luminescent properties. Compound 1 behaves as a field-induced Single Molecule Magnet (SMM) and presents temperature-dependent luminescence characteristics of Eu making it an emissive thermometer working in the temperature range 293-373 K with the maximum relative sensitivity of 1.

Chemometrics in Protein Formulation: Stability Governed by Repulsion and Protein Unfolding.

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients.

Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice.

Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations.

Genome variability of domestic tomato varieties: data from AFLP analysis.

Tomato Solanum lycopersicum L. is one of the main vegetable crops, accessions and cultivars of which are characterized by a low level of genomic polymorphism. Introgressive tomato breeding uses related wild Solanum species to improve cultivars for stress tolerance and fruit quality traits.

Dependence of the content of starch and reducing sugars on the level of expression of the genes of β-amylases StBAM1 and StBAM9 and the amylase inhibitor StAI during long-term low-temperature storage of potato tubers.

Solanum tuberosum L. is the most important non-grain starch crop with a potential yield of 38-48 t/ha and a starch content of 13.2-18.

Quantum-based Modeling of Protein-ligand Interaction: The Complex of RutA with Uracil and Molecular Oxygen.

Modern quantum-based methods are employed to model interaction of the flavin-dependent enzyme RutA with the uracil and oxygen molecules. This complex presents the structure of reactants for the chain of chemical reactions of monooxygenation in the enzyme active site, which is important in drug metabolism. In this case, application of quantum-based approaches is an essential issue, unlike conventional modeling of protein-ligand interaction with force fields using molecular mechanics and classical molecular dynamics methods.

Dynamics of Human Serum Transferrin in Varying Physicochemical Conditions Explored by Using Molecular Dynamics Simulations.

Conformational stability of human serum transferrin (Tf) at varying pH values and salt and excipient concentrations were investigated using molecular dynamics (MD) simulations, and the results are compared with previously published small-angle X-ray scattering (SAXS) experiments. SAXS study showed that at pH 5, Tf is predominantly present in a partially open (PO) form, and the factions of PO differ based on the physicochemical condition and drift toward the closed form (HO) as the pH increases. Tf is a bilobal glycoprotein that is composed of homologous halves termed the N- and C-lobes.

Temperature sensing in Tb/Eu-based tetranuclear silsesquioxane cages with tunable emission.

New luminescent cage-like tetranuclear silsesquioxanes [NEt][(PhSiO)(TbEu)(NO)(OH)(EtOH)(HO)]·4(EtOH) (1) and [NEt][(PhSiO)(TbEu)(NO)(EtOH)(MeCN)]·4(MeCN) (2) present a tunable thermosensitive Tb-to-Eu energy transfer driven by Tb and Eu emission and may be used as temperature sensors operating in the range 41-100 °C with excellent linearity ( = 0.9990) and repeatability (>95%). The thermometer performance was evidenced by the maximum relative sensitivity of 0.

Investigation of the pH-dependent aggregation mechanisms of GCSF using low resolution protein characterization techniques and advanced molecular dynamics simulations.

Granulocyte-colony stimulating factor (GCSF) is a widely used therapeutic protein to treat neutropenia. GCSF has an increased propensity to aggregate if the pH is increased above 5.0.

Chirality transmission in macromolecular domains.

Chiral communications exist in secondary structures of foldamers and copolymers via a network of noncovalent interactions within effective intermolecular force (IMF) range. It is not known whether long-range chiral communication exists between macromolecular tertiary structures such as peptide coiled-coils beyond the IMF distance. Harnessing the high sensitivity of single-molecule force spectroscopy, we investigate the chiral interaction between covalently linked DNA duplexes and peptide coiled-coils by evaluating the binding of a diastereomeric pair of three DNA-peptide conjugates.

Combination of high throughput and structural screening to assess protein stability - A screening perspective.

High throughput screening for measuring the stability of industrially relevant proteins and their variants is necessary for quality assessment in the development process. Advances in automation, measurement time and sample consumption for many techniques allow rapid measurements with minimal amount of protein. However, many methods include automated data analysis, potentially neglecting important aspects of the protein's behavior in certain conditions.

[Molecular mechanism of chromogenic substrate hydrolysis in the active site of human carboxylesterase-1].

Human carboxylesterases are involved in the protective processes of detoxification during the hydrolytic metabolism of xenobiotics. Knowledge of the molecular mechanisms of substrates hydrolysis in the enzymes active site is necessary for the rational drug design. In this work, the molecular mechanism of the hydrolysis reaction of para-nitrophenyl acetate in the active site of human carboxylesterase was determined using modern methods of molecular modeling.

Light-Induced Change of Arginine Conformation Modulates the Rate of Adenosine Triphosphate to Cyclic Adenosine Monophosphate Conversion in the Optogenetic System Containing Photoactivated Adenylyl Cyclase.

We report the first computational characterization of an optogenetic system composed of two photosensing BLUF (blue light sensor using flavin adenine dinucleotide) domains and two catalytic adenylyl cyclase (AC) domains. Conversion of adenosine triphosphate (ATP) to the reaction products, cyclic adenosine monophosphate (cAMP) and pyrophosphate (PPi), catalyzed by ACs initiated by excitation in photosensing domains has emerged in the focus of modern optogenetic applications because of the request in photoregulated enzymes that modulate cellular concentrations of signaling messengers. The photoactivated AC from the soil bacterium sp.

A Multi-Method Approach to Assess the Self-Interaction Behavior of Infliximab.

Attractive self-interaction processes in antibody formulations increase the risk of aggregation and extraordinarily elevated viscosity at high protein concentrations. These challenges affect manufacturing and application. This study aimed to understand the self-interaction process of Infliximab as a model system with pronounced attractive self-interaction.

New Luminescent Tetranuclear Lanthanide-Based Silsesquioxane Cage-Like Architectures.

Invited for the cover of this issue are Alexey N. Bilyachenko, Joulia Larionova and co-workers at the Russian Academy of Sciences, the Peoples' Friendship University of Russia, and University of Montpellier. The image depicts lanthanide-based cage-like silsesquioxanes exhibiting magnetic and luminescence properties that could constitute a particularly interesting new family related to multifunctional nanomaterials.

New Luminescent Tetranuclear Lanthanide-Based Silsesquioxane Cage-Like Architectures.

The synthesis, structure, magnetic, and luminescence properties investigations of four new cage-like lanthanide-based silsesquioxanes (Cat) [(PhSiO ) (LnO ) (O)(NO ) (EtOH) (MeCN) ] (where Cat =Et N , PPh P and Ln =Eu , Tb and (Ph P) [(PhSiO ) (TbO ) (O) (NO ) ]â‹…10MeCN are reported. They present an unusual prism-like topology of cage architectures and lanthanide-characteristic emission, which makes them the first luminescent cage-like lanthanide silsesquioxanes. One of the Tb -based cages presents a magnetic spin-flip transition.

Small angle X-ray scattering and molecular dynamic simulations provide molecular insight for stability of recombinant human transferrin.

Unlabelled: Transferrin is an attractive candidate for drug delivery due to its ability to cross the blood brain barrier. However, in order to be able to use it for therapeutic purposes, it is important to investigate how its stability depends on different formulation conditions. Combining high-throughput thermal and chemical denaturation studies with small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, it was possible to connect the stability of transferrin with its conformational changes.