Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

Recently, a new variant, B.1620, with mutations (S477N-E484K) in the spike protein’s receptor-binding domain (RBD) has been reported in Europe. In order to design therapeutic strategies suitable for B.1.620, further studies are required. A detailed investigation of the structural features and variations caused by these substitutions, that is, a molecular level investigation, is essential to uncover the role of these changes. To determine whether and how the binding affinity of ACE2–RBD is affected, we used protein–protein docking and all-atom simulation approaches. Our analysis revealed that B.1.620 binds more strongly than the wild type and alters the hydrogen bonding network. The docking score for the wild type was reported to be −122.6 +/− 0.7 kcal/mol, while for B.1.620, the docking score was −124.9 +/− 3.8 kcal/mol. A comparative binding investigation showed that the wild-type complex has 11 hydrogen bonds and one salt bridge, while the B.1.620 complex has 14 hydrogen bonds and one salt bridge, among which most of the interactions are preserved between the wild type and B.1.620. A dynamic analysis of the two complexes revealed stable dynamics, which corroborated the global stability trend, compactness, and flexibility of the three essential loops, providing a better conformational optimization opportunity and binding. Furthermore, binding free energy revealed that the wild type had a total binding energy of −51.14 kcal/mol, while for B.1.628, the total binding energy was −68.25 kcal/mol. The current findings based on protein complex modeling and bio-simulation methods revealed the atomic features of the B.1.620 variant harboring S477N and E484K mutations in the RBD and the basis for infectivity. In conclusion, the current study presents distinguishing features of B.1.620, which can be used to design structure-based drugs against the B.1.620 variant.

Inhibitory Reactivity of Capsaicin with α-Amylase and α-Glucosidase Related to Antidiabetes using Molecular Docking and Quantum Calculation Methods

This work aims to investigate the inhibitory activity of capsaicin, which is one of capsaicinoid compounds, on these enzymes using a molecular docking and quantum calculation. Acarbose, a commercial diabetes drug, was also investigated for comparison. The docking results revealed that acarbose yields better inhibition efficiency with binding free energy (ΔGbinding) of about -8.2 to -11.9 kcal/mol, and inhibition constant (Ki) of about 0.0002 to 0.4 µM, whereas capsaicin provided the ΔGbinding of -5.8 to -6.1 kcal/mol and Ki of 23.7 to 45.9 µM. The total binding energy (ΔEbinding) between each inhibitor and amino acids in active site of enzyme obtained from quantum calculation with MP2/6-31G(d,p) level is in agreement with the ΔGbinding, i.e. the ΔEbinding of acarbose was larger negative than that of capsaicin. The amino acids interacting with inhibitor as hydrogen bond mainly contribute to the total binding energy. Nevertheless, it could be concluded that capsaicinoids have high potential to be developed as an alternative drug for diabetes disease.

Binding of Industrial Deposits of Heavy Metals and Arsenic in the Soil by 3-Aminopropyltrimethoxysilane

The results of the research studies concerning binding of heavy metals and arsenic (HM+As), occurring in soils affected by emissions from Głogów Copper Smelter and Refinery, by silane nanomaterial have been described. The content of heavy metals and arsenic was determined by AAS and the effectiveness of heavy metals and arsenic binding by 3-Aminopropyltrimethoxysilane was examined. The total leaching level of impurities in those fractions was 73.26% Cu, 74.7% – Pb, 79.5% Zn, 65.81% – Cd and 55.55% As. The studies demonstrated that the total binding of heavy metals and arsenic with nanomaterial in all fractions was about as follows: 20.5% Cu, 9.5% Pb, 7.1% Zn, 25.3% Cd and 10.89% As. The results presented how the safety of food can be cultivated around industrial area, as the currently used soil stabilization technique of HM by soil pH does not guarantee their stable blocking in a sorptive complex.

Interactions of 2,2′-bipyridine herbicide intermediate with humic acid

The binding of the neutral 2,2′-bipyridine (BP) molecule to solid humic acid (HA) was studied in the presence of CaCl2 background electrolyte (10-2 mol/l), at pH=6.1–6.3. To investigate the binding, two different methods were used: the well-established static adsorption equilibrium measurements and the technique of equilibrium dialysis (ED). The obtained isotherms were fitted by the Langmuir equation, yielding values for the total binding capacity (qT) and the Langmuir constant (K). The values obtained from the batch experiment were: qT=3.3×10-4 mol/gHA, K=4.1×102 l/mol and from the ED experiment were: qT=5.7×10-4 mol/gHA, K=2.8×102 l/mol. From the linear range of the isotherm, the value of the distribution coefficient KD was calculated as 3.3×102 l/kgHA (by both methods). This parameter was used to calculate the value of KOC: 6.6×102 l/kgOC, indicating that BP is a slightly mobile pollutant in the HA dominated soil.

EXTENDED SKYRME INTERACTION IN THE SPIN CHANNEL

Most of the Skyrme interactions are known to predict spin or isospin instabilities beyond the saturation density of nuclear matter which contradict predictions based on realistic interactions. A modification of the standard Skyrme interaction is proposed so that the ferromagnetic instability is removed. The new terms are density dependent and modify only the spin p - h interaction in the case of spin-saturated system. We have shown that these new terms change the total binding energy of odd-nuclei by only few tenths of keV. From the analysis of the spin instabilities of nuclear matter, restrictions on the parameters governing the spin-density dependent terms are evaluated. We conclude that with the extended Skyrme interaction, the Landau parameters G0 and [Formula: see text] could be tuned with a large flexibility without changing the ground-state properties in nuclei and in nuclear matter.

NEW CALCULATION FOR SOME GROUND STATE FEATURES OF 40Ca, 48Ca32S AND 39K NUCLEI

Some ground states features of 32 S , 39 K , 40 Ca and 48 Ca nuclei are investigated using the Hartree–Fock method with the Skyrme SKM * and SLy4 forces calculated in two different code implementations. The calculated total binding energies per particle and root mean square (rms) nuclear charge radii using the Skyrme–Hartree–Fock (SHF) + BCS method are compared with relativistic mean-field (RMF) theory and experimental values. The obtained charge density distributions from these code implementations are compared with the experimental data. Pairing effects are also included in calculations for the same nuclei. Variations of the total binding energies per particle and rms nuclear charge radii were investigated as the last shell nucleons were carried to the upper shell.

GLOBAL NUCLEAR STRUCTURE ASPECTS OF TENSOR INTERACTION

A direct fit of the isoscalar spin-orbit and both isoscalar and isovector tensor coupling constants to the f5/2 - f7/2 SO splittings in 40 Ca , 56 Ni , and 48 Ca requires (i) a significant reduction of the standard isoscalar spin-orbit strength and (ii) strong attractive tensor coupling constants. The aim of this paper is to address the consequences of these strong attractive tensor and weak spin-orbit fields on total binding energies, two-neutron separation energies and nuclear deformability.

THE ppK− SYSTEM STUDIED WITH A CHIRAL SU(3) BASED $\bar{K}N$ POTENTIAL

We have investigated the prototype of [Formula: see text]-nuclear systems, ppK−, with a realistic NN potential and effective local [Formula: see text] potentials based on chiral SU (3) dynamics. Including estimates of theoretical uncertainties, we find that ppK− is not deeply bound, with a total binding energy = 19 ± 3 MeV and mesonic decay width between about 40 and 70 MeV. The [Formula: see text] component in the ppK− compound is of a similar structure as the [Formula: see text] two-body quasibound state embedded in the πΣ continuum.

DNA Binding of Iron(II)-Phenanthroline Complexes: Effect of Methyl Substitution on Thermodynamic Parameters

The influence of methyl substitution on the thermodynamic parameters for the binding of [Fe(DMP)3]2+ and [Fe(TMP)3]2+ (DMP = 4,7-dimethyl-1,10-phenanthroline, TMP = 3,4,7,8-tetramethyl- 1,10-phenanthroline) to calf thymus DNA (ct-DNA) has been studied by determining their equilibrium binding constants (Kb) at various salt concentrations and temperatures. Kb of the iron(II) complexes to ct-DNA decreases with the salt concentration in the solution, suggesting considerable electrostatic interaction in the ct-DNA binding of the iron(II) complexes. In contrast, Kb of the DNA binding increases with temperature, indicating that the DNA binding reaction of the complex is endothermic and entropically driven. The evaluation of the non-electrostatic binding constant (K0t) based on polyelectrolyte theory has revealed that the K0t portions of the total binding constant (Kb) are relatively large and reach 46.4% for [Fe(DMP)3]2+ at [Na+] = 0.075 M and 43.9% for [Fe(TMP)3]2+ at [Na+] = 0.100 M. The contribution of non-electrostatic binding free energy (ΔG0t ) to total binding free energy change (ΔG0) is extremely large, i. e. > 90% for both iron(II) complexes at [Na+] = 0.05 M, suggesting that the stabilization of the DNA binding is mainly contributed from the non-electrostatic process. The effect of methyl substitution on electrostatic (ΔG0pe) and non-electrostatic (ΔG0t ) binding free energy changes has been systematically evaluated using the quantity of ΔΔG0pe and ΔΔG0t relative to that of the parent iron(II) complex, [Fe(phen)3]2+. The results indicate that the substitution of hydrogen atoms in the phen ligand by methyl groups decreases slightly the electrostatic binding free energy changes, but tremendously increases the non-electrostatic ones to yield net binding free energy changes which are more favorable for the ct-DNA binding.