Conformational Flexibilities and Solvation Properties of Insulin in Aromatic Amino Acid Solutions: A Molecular Dynamics Study Using CHARMM Drude Polarizable Model

Aromatic amino acids (AAA) play a crucial role in the structure and function of proteins. A higher level of AAA causes several diseases, controls insulin levels. In this work, we carried out atomistic molecular dynamics simulations by using CHARMM Drude polarizable force field to investigate the conformational properties of insulin monomer in 2M phe, tyr, trp solutions as well as in pure aqueous solution to compare the relative changes of protein conformations, its solvation properties and the interactions of the free AAA with insulin. Although insulin’s native folded form was intact in all the solutions within the simulation length scale, we observed that the protein is a little more flexible and less compact in phe solution than in tyr/trp solutions. The free AAAs identified to self-aggregate around the protein surface and form clusters of different sizes. They interacted with insulin, significantly through cation/anion–[Formula: see text] and [Formula: see text]–[Formula: see text] stacking, and partly through hydrogen bonded interactions. Among the three, trp was prone to interact through cation–[Formula: see text] interactions while phe and tyr interacted through [Formula: see text]–[Formula: see text] stacking with insulin. Despite a significant number of free AAA molecules in the solvation shell, insulin was observed to be sufficiently hydrated and formed hydrogen bonds with water. Some of our findings agreed with the available experimental results that establish the reliability of the chosen force field. Our findings would interpret the interactions between the free AAA and insulin in solution, helpful to recognize the microscopic details of AAA governed biological processes in living organisms.

Enhancing the Methanol Tolerance of Candida antarctica Lipase B by Saturation Mutagenesis for Biodiesel Preparation

Methanol tolerance of a lipase is one of the important factors affecting its esterification ability in biodiesel preparation. By B factor indicated prediction of Candida antarctica lipase B (CalB) surface amino acids, 8 sites (Val139, Ala146, Leu147, Pro218, Val286, Ala287, Val306, and Gly307) with high B value indicating more flexibility were chosen to perform saturation mutagenesis. High-methanol-tolerant variants, CalB-P218W and -V306N, created larger haloes on emulsified tributyrin solid plate including 15% (v/v) methanol and showed 19% and 31% higher activity over CalB-WT (wild type), respectively. By modeling, a newly formed hydrogen bond in CalB-V306N and hydrophobic force in CalB-P218W contributing more stability in protein may have resulted in increased methanol tolerance. CalB-P218W and -V306N transesterified the soybean oil into biodiesel at 30 °C by 85% and 89% yield, respectively, over 82% by CalB-WT for 24 h reactions. These results may provide a basis for molecular engineering of CalB and expand its applications in fuel industries. The as-developed semi-rational method could be utilized to enhance the stabilities of many other industrial enzymes.

Wear Resistance of Spark Ignition Engine Piston Rings in Hydrogen-Containing Environments

We describe the external and internal hydrogen iInteraction on contacting surfaces in the “cylinder–piston rings” friction coupling. Under the influence of high temperatures and pressure, the oil in the combustion chamber at a temperature up to 1473 K decomposes and forms small amounts of water. External hydrogen (H2) is subsequently formed. Hydrogen removal from the piston rings reduces the heterogeneity of the structure, residual stresses, and uneven physical and chemical properties of the near-surface layers, which reduces the stress concentration and, as a consequence, results in an improvement in the performance characteristics of the surface layers of the friction couple “cylinder-piston rings” of the spark ignition engine.

Engineering of a thermophilic dihydroxy-acid dehydratase to enhance its dehydration ability on glycerate to pyruvate and its application in in vitro synthetic enzymatic biosystems

The low activity of dihydroxy-acid dehydratase (DHAD) on dehydration of glycerate to pyruvate hampers its applications in the biosystems. Protein engineering of a thermophilic DHAD from Sulfolobus solfataricus (SsDHAD) was performed to increase its dehydratation activity. A novel high-throughput method was established. A triple-mutant (I161M/Y145S/G205K) with a 10-fold higher activity on glycerate dehydration was obtained after three rounds of iterative saturation mutagenesis (ISM) based on computational analysis. The shrunk substrate-binding pocket and newly formed hydrogen bonds were the reason for the activity improvement of the mutant. For the in vitro synthetic enzymatic biosystems of converting glucose or glycerol to L-lactate, the biosystems with the mutant SsDHAD showed 3.32- and 2.34-times of the reaction rate than that of wild type, respectively. This study demonstrates the potential of protein engineering to improve the efficiency of in vitro synthetic enzymatic biosystems by enhancing the enzyme activity of rate-limited enzymes.

The role of hydrogen bonds in diluted ethanol solutions of cyclohexane and dimethylformamide

The aim of this work is to determine molecular association in solutions of cyclohexane-ethanol and dimethylformamide-ethanol. The refractometric method and Fourier transform infrared spectroscopy used to determine the optical features of the concentration characteristics of diluted ethanol solutions of cyclohexane and dimethylformamide. It was found for the first time that at some concentrations the hydrogen bond is stronger than for a pure ethanol solution. The first maximum of the excess refractive index of solutions is formed at a concentration of 0.02 mole fraction of cyclohexane and dimethylformamide, which is in good correlation with IR spectroscopy, indicating the largest number of formed hydrogen bonds.

Modulation of Mn3+ Spin State by Guest Molecule Inclusion

Spin state preferences for a cationic Mn3+ chelate complex in four different crystal lattices are investigated by crystallography and SQUID magnetometry. The [MnL1]+ complex cation was prepared by complexation of Mn3+ to the Schiff base chelate formed from condensation of 4-methoxysalicylaldehyde and 1,2-bis(3-aminopropylamino)ethane. The cation was crystallized separately with three polyatomic counterions and in one case was found to cocrystallize with a percentage of unreacted 4-methoxysalicylaldehyde starting material. The spin state preferences of the four resultant complexes [MnL1]CF3SO3·xH2O, (1), [MnL1]PF6·xH2O, (2), [MnL1]PF6·xsal·xH2O, (2b), and [MnL1]BPh4, (3), were dependent on their ability to form strong intermolecular interactions. Complexes (1) and (2), which formed hydrogen bonds between [MnL1]+, lattice water and in one case also with counterion, showed an incomplete thermal spin crossover over the temperature range 5–300 K. In contrast, complex (3) with the BPh4−, counterion and no lattice water, was locked into the high spin state over the same temperature range, as was complex (2b), where inclusion of the 4-methoxysalicylaldehyde guest blocked the H-bonding interaction.

CONDITIONS OF FORMATION OF SULFIDE WATERS IN PARAGENESIS WITH EVAPORITE AND OIL AND GAS-BASED FORMATIONS IN THE ARTESIAN POOLS OF THE REPUBLIC OF UZBEKISTAN

The lithological-facies factor is considered with the aim of studying the natural and geological conditions in which hydrogen sulfide waters are formed in gas and oil fields in the artesian basins of the Republic of Uzbekistan. The distribution of hydrogen sulfide waters is closely related to the areas of joint development of halogen rocks and oil and gas complexes. Since the term “paragenesis” refers to the joint finding of minerals or chemical elements genetically related, this map is a map of the paragenesis of hydrogen sulfide waters with evaporites and oil and gas complexes. In the absence of one of the necessary conditions (sulfates or petroleum organics), hydrogen sulfide waters of high concentration are not formed. Hydrogen sulfide waters in the identified anticlinal structures are formed due to the presence of insignificant gas and oil deposits, which are not of industrial importance

Rutin as a Promising Inhibitor of Main Protease and Other Protein Targets of COVID-19: In Silico Study

The process of investigating a possible cure for coronavirus disease 2019 (COVID-19) in vitro and in vivo may take a long time. For this reason, several in silico studies were performed in order to produce preliminary results that could lead to treatment. Extract of Juniperus procera Hochst is used as a traditional medicine for recovery from flu in Saudi Arabia. In the present study, more than 51 phytochemicals of J. procera were docked against the main protease of COVID-19. Rutin gave the highest interaction score among all the phytochemicals and the commercially available antiviral drugs. Lopinavir showed the second highest binding score. Rutin and lopinavir were further investigated using homology models of COVID-19. Rutin showed a better inhibition score in 9 of the 11 of homology models compared with lopinavir. Analysis of ligand-protein interaction contacts revealed that 3 residues (Glu166, Gly143, and Thr45) of the main protease formed hydrogen bonds with rutin. This simulation study suggests that rutin could be a possible effective inhibitor of several COVID-19 protein targets, including the main protease. Rutin, already available for commercial use, was evaluated for its ability as a possible drug. To our knowledge, this is the first study that suggests rutin having a possible strong inhibitory role against several protein targets of COVID-19.

Influence of the Molecular Weight and the Presence of Calcium Ions on the Molecular Interaction of Hyaluronan and DPPC

Hyaluronan is an essential physiological bio macromolecule with different functions. One prominent area is the synovial fluid which exhibits remarkable lubrication properties. However, the synovial fluid is a multi-component system where different macromolecules interact in a synergetic fashion. Within this study we focus on the interaction of hyaluronan and phospholipids, which are thought to play a key role for lubrication. We investigate how the interactions and the association structures formed by hyaluronan (HA) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) are influenced by the molecular weight of the bio polymer and the ionic composition of the solution. We combine techniques allowing us to investigate the phase behavior of lipids (differential scanning calorimetry, zeta potential and electrophoretic mobility) with structural investigation (dynamic light scattering, small angle scattering) and theoretical simulations (molecular dynamics). The interaction of hyaluronan and phospholipids depends on the molecular weight, where hyaluronan with lower molecular weight has the strongest interaction. Furthermore, the interaction is increased by the presence of calcium ions. Our simulations show that calcium ions are located close to the carboxylate groups of HA and, by this, reduce the number of formed hydrogen bonds between HA and DPPC. The observed change in the DPPC phase behavior can be attributed to a local charge inversion by calcium ions binding to the carboxylate groups as the binding distribution of hyaluronan and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine is not changed.