Van Der Waals Energy Research Articles

In-silico identification of potential inhibitors against FabI protein in Klebsiella pneumoniae

The development of new antimicrobial drugs is needed to combat multi-drug resistant and novel hypervirulent strains of Klebsiella pneumoniae (KPN) that are associated with increased morbidity and mortality globally. The FabI protein plays a crucial role in fatty acid biosynthesis and has been identified as an important target for in-silico, in-vitro, and in-vivo drug discovery. In this study we have used computer integrated-drug discovery approaches and binding-free energy calculations to identify three novel inhibitors (21272541, 67724550, and 67724551) of the FabI protein. All inhibitors showed strong affinity including van der Waals energy, electrostatic energy, polar and non-polar energies; however, the 21272541 compound was the most effective inhibitor and bound with the strongest affinity (ΔGbind −59.02 kcal/mol) to the FabI protein. Nevertheless, all three inhibitors are promising targets for new novel antimicrobial drugs that could contribute to the management of antimicrobial resistant KPN infections based on various computational analysis. Additional in-vitro and in-vivo clinical studies will be needed to confirm drug effectiveness for the treatment of KPN infections.

An Insight of Cryptocarya Secondary Metabolites as Anticancer P388: Study of Molecular Docking and ADMET Properties

Secondary metabolites isolated from Cryptocarya was known to have various activity especially their cytotoxicity in P388 cell. There were two species of Cryptocarya studied in this research that were Cryptocarya konishii and Cryptocarya lucida. In both species, 8 isolate compounds had bioactivity as anticancer in P388 cells. This study aimed to know the binding affinity and ADMET properties of each isolated compound through P-glycoprotein substrate since this protein was reported to be responsible for the inhibition of P388 cells. Molecular docking was performed using AutoDock4 and AutoDockTools software to know the binding energy and interaction of isolate compounds against the P-glycoprotein substrate. ADMET properties calculation was done using the pkCSM web server for all compounds. Molecular docking results showed that Kurzichalcolactone B (7) isolated from C. lucida had the lowest binding energy. It resulted in the highest total intermolecular energy from the contribution of van der Waals and hydrogen bond energy. The lowest binding energy is indicating the stable interaction of ligand and substrate. Calculation of ADMET properties resulted that some of the isolate compounds fulfilling the minimum standard parameters in ADMET properties.

Isolation of Genes Encoding for Human Epidermal Growth Factor (hEGF) from Human Blood: In Vitro and In Silico Study

The 6.12 kDa human epidermal growth factor (hEGF) protein is expressed in the body and plays a role in cell proliferation and differentiation. This research aims to isolate the hEGF genes, determine the phylogenetic relationship between organisms based on the hEGF gene, construct the 3D structure of the hEGF protein, and identify the precise binding position between the hEGF protein and the tested Myosin-9. DNA was isolated from blood of healthy individuals followed by amplification using specified primers. DNA sequencing was utilized to identify the amplification results before generating the phylogenetic trees. The retrieved sequences were then modeled using the Swiss model and docking proteins in silico. In three samples, DNA was successfully amplified to 700 bp and the phylogenetic analysis revealed that the three hEGF gene samples belonged to the same clades. With a 30 % identity seq, aligned result sequences modeled using the Swiss model created proteins which were not homologous. The outcomes of this modeling were compared to the hEGF protein from the database, which had a sequence identity of greater than 90 %. The i-RMSD value of the target protein (5.4 +/- 0.4), the Van der Waals energy (-29.3 +/- 1.7), and the Z-score were determined by simulation (-1.7). These results indicate a potential interaction between the isolated EGF protein and the myosin-9 tested. HIGHLIGHTS Human Epidermal Growth Factor (hEGF) protein is a potential protein expressed in the body and plays a role in cell proliferation and differentiation Isolation of the EGF gene through human blood can be carried out to get data on protein size, phylogenetic analysis, and protein structure The results of in vitro study were modeled in silico to obtain the three-dimensional structure as well as intermolecular interactions of the protein Information beginning this study is used in follow-up research to predict EGF communications with other molecules GRAPHICAL ABSTRACT

Electron-Phonon Interaction Contribution to the Total Energy of Group IV Semiconductor Polymorphs: Evaluation and Implications.

In density functional theory (DFT)-based total energy studies, the van der Waals (vdW) and zero-point vibrational energy (ZPVE) correction terms are included to obtain energy differences between polymorphs. We propose and compute a new correction term to the total energy, due to electron-phonon interactions (EPI). We rely on Allen's general formalism, which goes beyond the quasi-harmonic approximation (QHA), to include the free energy contributions due to quasiparticle interactions. We show that, for semiconductors and insulators, the EPI contributions to the free energies of electrons and phonons are the corresponding zero-point energy contributions. Using an approximate version of Allen's formalism in combination with the Allen-Heine theory for EPI corrections, we calculate the zero-point EPI corrections to the total energy for cubic and hexagonal polytypes of carbon, silicon and silicon carbide. The EPI corrections alter the energy differences between polytypes. In SiC polytypes, the EPI correction term is more sensitive to crystal structure than the vdW and ZPVE terms and is thus essential in determining their energy differences. It clearly establishes that the cubic SiC-3C is metastable and hexagonal SiC-4H is the stable polytype. Our results are consistent with the experimental results of Kleykamp. Our study enables the inclusion of EPI corrections as a separate term in the free energy expression. This opens the way to go beyond the QHA by including the contribution of EPI on all thermodynamic properties.

Investigation of the adhesion and debonding behaviors of rubber asphalt and aggregates using molecular dynamics simulation

This paper investigates the interface property between rubber asphalt and aggregates using molecular dynamics simulations to address the adhesion and debonding properties. The effect of aggregate types and rubber contents on rubber asphalt-aggregate systems' adhesion and debonding properties were investigated. The work of adhesion characterized the adhesion property while debonding characteristics were evaluated by the work of debonding and energy ratio (ER). The results show that the impact of aggregate types on the adhesion and debonding between rubber asphalt and aggregates is much more significant than rubber contents. The work of adhesion between four aggregates and rubber asphalt is evaluated as follows: microcline > albite > quartz > calcite. The reason is that the electrostatic energy can considerably contribute to the adhesion at the interface for strong alkali aggregates (microcline, albite) and rubber asphalt, while the van der Waals energy can only contribute nearly 100 mJ/m2 energy for the adhesion. The work of debonding for the four aggregates with rubber asphalt follows the order: microcline > quartz > albite > calcite. Therefore, microcline presents extraordinary performance, while calcite shows the poorest response in moisture resistance.

Spherical PEG/SiO2 promising agents for Lamivudine antiviral drug delivery, a molecular dynamics simulation study

Spherical nanocarriers can lead to a bright future to lessen problems of virus infected people. Spherical polyethylene glycol (PEG) and spherical silica (SiO2) are novel attractive nanocarriers as drug delivery agents, especially they are recently noticed to be reliable for antiviral drugs like anti-HIV, anti-covid-19, etc. Lamivudine (3TC) is used as a first line drug for antiviral therapy and the atomic view of 3TC-PEG/SiO2 complexes enable scientist to help improve treatment of patients with viral diseases. This study investigates the interactions of 3TC with Spherical PEG/SiO2, using molecular dynamics simulations. The mechanism of adsorption, the stability of systems and the drug concentration effect are evaluated by analyzing the root mean square deviation, the solvent accessible surface area, the radius of gyration, the number of hydrogen bonds, the radial distribution function, and Van der Waals energy. Analyzed data show that the compression of 3TC is less on PEG and so the stability is higher than SiO2; the position and intensity of the RDF peaks approve this stronger binding of 3TC to PEG as well. Our studies show that PEG and also SiO2 are suitable for loading high drug concentrations and maintaining their stability; therefore, spherical PEG/SiO2 can reduce drug dosage efficiently.

Molecular dynamics simulation of phosphatidylcholine membrane in low ionic strengths of sodium chloride

The one-microsecond molecular dynamics simulations of a membrane-protein complex investigate the influence of the aqueous sodium chloride solutions on the structure and dynamics of a palmitoyl-oleoyl-phosphatidylcholine bilayer membrane. The simulations were performed on five different concentrations (40, 150, 200, 300, and 400 mM) in addition to a salt-free system by using the charmm36 force field for all atoms. Four biophysical parameters, (membrane thicknesses of annular and bulk lipids, and the area per lipid of both leaflets), were computed separately. Nevertheless, the area per lipid was expressed by using the Voronoi algorithm. All time-independent analyses were carried out for the last 400 ns trajectories. Different concentrations revealed dissimilar membrane dynamics before equilibration. The biophysical properties of the membrane (thickness, area-per-lipid, and order parameter) have non-significant changes with increasing ionic strength, however, the 150 mM system had exceptional behavior. Sodium cations were dynamically penetrating the membrane forming weak coordinate bonds with single or multiple lipids. Nevertheless, the binding constant was unaffected by the cation concentration. The electrostatic and Van der Waals energies of lipid-lipid interactions were influenced by the ionic strength. On the other hand, the Fast Fourier Transform was performed to figure out the dynamics at the membrane-protein interface. The nonbonding energies of membrane-protein interactions and order parameters explained the differences in the synchronization pattern. All results were consensus with experimental and theoretical works.Communicated by Ramaswamy H. Sarma

Investigation of wax inhibition efficiency based on alkane structures in model asphalt for sustainable utilization of wax inhibitors

In recent years, the wax inhibitors (WIs) are used to inhibit premature crystallization of alkane molecules in asphalt at low temperatures has yielded certain benefits. However, the method for effective and sustainable use of WIs in asphalt to avoid inefficient and expensive “trial and error” procedures has not yet been determined. In this paper, the model asphalts were established through non-waxy base asphalt doped with n-alkanes (Eicosane, triacontane and tetradecane) and isoalkane (Squalene), and the wax inhibition efficiencies and cracking resistance of model asphalt with addition of three typical WIs (poly (methyl methacrylate) (PMMA), nano-SiO2 hybrid PMMA and ionic liquid (IL) modified with graphene oxide (GO)) were directly characterized by wax precipitation temperature (WPT) and extended bending beam rheometer (Ex-BBR), double edge notched tension (DENT) and thermal fatigue tests, respectively. On this basis, the microscopic mechanism of wax inhibition was investigated by molecular dynamic simulation. The results show that the wax inhibition efficiencies are higher for the short-chain n-alkanes and ordered isoalkanes to improve the low-temperature cracking, ductile and thermal fatigue resistances more significantly, but the disordered isoalkanes and high content of long-chain n-alkanes will decrease the wax inhibition efficiencies of WIs. The WIs can increase diffusion coefficient and bond stretching, angle bending and dihedral angle torsion energies but decrease the Coulomb and van der waals (VDW) energies of wax molecules to inhibit the formation of wax crystals network. It is recommended to add WIs with higher content or efficiency for asphalts with heavy n-paraffins and low concentration of branched paraffins to inhibit wax precipitation. As for asphalts containing light n-alkanes and high concentration of branched alkanes, it is suggested to add smaller amount of WIs to save resources.

Computational assessment of chemicals from Morinda citrifolia as potential inhibitors of B-Raf kinase in hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC) is a tumour pathology that lacks specific treatment and is predominantly resistant to chemotherapy. The inhibitory activity of Morinda citrifolia, an evergreen tree commonly called Noni, against various carcinomas especially HCC is widely acclaimed. This study was to assess the phytochemical constituents of the plant for inhibitory activity against B-Raf kinase (3C4C) in order to design drugs for HCC treatment. Molecular docking, pharmacophore modelling, induced-fit docking, molecular dynamics (MD) simulations and ADMET predictions were the computational techniques employed in this study to detect potential inhibitors of B-Raf kinase from 135 compounds of Morinda citrifolia. Soranjidiol, Thiamine, Lucidin, 2-Methyl-1,3,5-Trihydroxyanthraquinone and Rubiadin were the five top-scoring compounds ranging from −8.39 to −8.22 kcal/mol, however, the standard ligand, PLX4720, scored −11.26 kcal/mol. The five compounds, like PLX4720 demonstrated hydrogen bond interactions with active site amino acid residues such as GLN 530, CYS 532 and ASP 594. The main energy contributor to the interactions between the compounds and B-Raf kinase were pi-stacking, hydrogen bond, van der Waals and covalent energy. Better docking scores obtained in the induced-fit docking further validates the inhibitory potential of the Soranjidiol against the flexible protein. In MD simulations, Soranjidiol revealed good stability in the active site of the protein since significant conformational changes were not evident. These five compounds, unlike the standard compound, demonstrated adequate druglike properties and good safety profiles. Therefore, further studies should be undertaken so as to develop them into drugs against HCC. Communicated by Ramaswamy H. Sarma

Interaction of Aggregated Cationic Porphyrins with Human Serum Albumin.

The interaction of an equilibrium mixture of monomeric and aggregated cationic trans-5,15-bis(N-methylpyridinium-4-yl)-10,15-bis-diphenylporphine (t-H2Pagg) chloride salt with human serum albumin (HSA) has been investigated through UV/Vis absorption, fluorescence emission, circular dichroism and resonant light scattering techniques. The spectroscopic evidence reveals that both the monomeric t-H2Pagg and its aggregates bind instantaneously to HSA, leading to the formation of a tight adduct in which the porphyrin is encapsulated within the protein scaffold (S430) and to clusters of aggregated porphyrins in electrostatic interaction with the charged biomolecules. These latter species eventually interconvert into the final S430 species following pseudo-first-order kinetics. Molecular docking simulations have been performed to get some insights into the nature of the final adduct. Analogously to hemin bound to HSA, the obtained model supports favorable interactions of the porphyrin in the same 1B subdomain of the protein. Hydrophobic and van der Waals energy terms are the main contributions to the calculated ΔGbind value of -117.24 kcal/mol.

Ceftriaxone induces glial EAAT-2 promotor region via NF-kB conformational changes: An interaction analysis using HADDOCK.

Excitotoxicity, depletion of energy metabolites, and ionic imbalance are the major factors involved in neurodegeneration mediated through excitatory amino acid transporter-2 (EAAT-2) dysfunction in ischemic insult. Recent studies have revealed that ceftriaxone expresses EAAT-2 via nuclear transcription factor kappa-B (NF-kB) signaling pathway, stimulation of EAAT-2 expression in the ischemic, and excitotoxic conditions that could provide potential benefits to control neurodegeneration. In this study, we have predicted the in silico model for interaction between NF-kB and EAAT-2 promoter region to rule out the conformational changes for the expression of EAAT-2 protein. Using homology-built model of NF-kB, we identified ceftriaxone-induced conformational changes in gene locus -272 of DNA where NF-kB binding with EAAT-2 promoter region through protein-DNA docking calculation. The interaction profile and conformational dynamics occurred between ceftriaxone predocked and postdocked conformations of NF-kB with DNA employing HADDOCK 2.2 web server followed by 250 ns long all atom explicit solvent molecular dynamics simulations. Both the protein and DNA exhibited modest conformational changes with respect to HADDOCK score, energy terms (desolvation energy [Edesolv ]), van der waal energy (Evdw ), electrostatic energy (Eelec ), restraints energy (Eair ), buried surface area, root mean square deviation, RMSF, radius of gyration, total hydrogen bonds when ceftriaxone pre- and postdocked NF-kB conformations were bound to DNA. Hence, the conformational changes in the C-terminal domain could be the reason for EAAT-2 expression through ceftriaxone specific binding pocket of -272 of DNA.

Bioadhesive Design Toward Renewable Composites: Adhesive Distribution and Molecular Adhesion

Improvements in renewable compositions of adhesives are key for advancing the existing wood industry and developing biocomposites. Building upon prior studies on fundamental interactions between model compounds of fiber and bioadhesives, more complex bioadhesives are investigated. Cold denaturation of soy protein isolate (SPI) in dilute sodium hydroxide provide sufficient physical strength for wood composites. Due to swelling, 5% epoxy resin is added to the SPI adhesive resulting in improved physical strength and water resistance. The SPI and epoxy are evenly distributed on the fiber surface, while additional SPI fills the gaps between fibers based on fluorescence microscopy and X‐ray photoelectron spectroscopy. Molecular dynamics (MD) simulations show that the physical strength of the composites increases with the content of SPI, with the number of hydrogen bonds (H‐bonds) as primary driver; in MD simulations, the composite strength is highest at 3% epoxy, though higher epoxy doses results in more H‐bonds. In ReaxFF MD simulations, other contributions (e.g., van der Waals energy) show no correlation. The developed bioadhesive and the interaction mechanism demonstrate here emphasize the weak physical interactions in these materials, though covalent bonds and other larger scale phenomena are important as well for macro performances of the bioadhesives.

Molecular dynamics and energy distribution of methane gas adsorption in shales

This study uses simulations to explore the energy distributions involved in the adsorption of methane gas in shales. Molecular mechanics calculations were carried out using the Forcite module in BIOVIA material studio software. The critical challenge in molecular-scale simulations remains the need to improve the description of the gas adsorption prior to up-scaling to a realistic scenario. Resolving this challenge requires the implementation of multi-scale techniques that employ atomistic/molecular-level results as input. Thus, it is pertinent that the appropriate molecular data on CH4 gas interaction with shale is obtained. This study provides empirical data on CH4 sorption/adsorption in shale at the molecular level to confirm the CH4 storage potential of shales. The effect of pressure on the CH4 sorption/adsorption was also investigated. A vital aspect of this study is elucidating the energy distribution and dominant energy that controls CH4 sorption/adsorption to serve as a basis for the exploitation of CH4 in productive shales. Following the intensive simulation exercise, the average total energy of CH4 sorption varied from approximately −30 to −120 kcal/mol with increase in pressure from 500 to 2500 psi, suggesting increasing thermodynamic stability. The results indicated that van der Waals energy is the major sorption energy with values ranging from 60 to −250 kcal/mol as the sorption pressure increased, while electrostatic energy recorded the least contribution. The total adsorption energy increased from −5 to −16 kcal/mol for reservoir pressure range of 1–15 MPa. This energy distribution data confirmed the possibility of CH4 adsorption on shale under reservoir pressure conditions.

Design of a novel multi-epitopes based vaccine against brucellosis

Brucella melitensis is a gram-negative coccobacillus that causes brucellosis in humans. The lack of effective treatment and increasing antibiotic-resistant patterns shown by B. melitensis, warrant the search for novel therapeutics. In this study, comprehensive bioinformatics, reverse vaccinology, and biophysics techniques were employed to design a novel multi-epitopes based vaccine (MEBV) against B. melitensis. Core proteomics, subtractive proteomics and immunoinformatic studies revealed three core proteins: Flagellar hook protein (FlgE), TonB-dependent receptor, and Porin family protein as promising vaccine targets. The proteins have exposed topology, and are antigenic, and adhesive. Furthermore, B and T cell epitopes were predicted from these proteins. Highly antigenic, immunogenic, non-toxic and non-allergenic epitopes were shortlisted and used in the MEBV design. The designed MEBV also showed stable docked conformation with different immune receptors such as MHC-I, MHC-II, and TLR-4. The global energy of selected docked complexes was as; solution 4 of MEBV-TLR-4 (−45.73 kJ/mol), solution 5 of MEBV-MHC-I (−20.94 kJ/mol), and solution 1 of MEBV-MHC-II (−3.45 kJ/mol). Molecular dynamics simulation studies unveiled a steady root mean square deviation (RMSD) pattern for the systems. However, all of them were stable in terms of intermolecular binding conformation and chemical interactions. Further, the systems showed robust binding energies with net binding energy < −300 kcal/mol. The van der Waals and electrostatic energies were the dominating energies and were found as intermolecular stabilizing factors. The vaccine was also predicted to generate promising immunological responses and thus could be an attractive candidate to be evaluated in experimental studies.

Structural Dynamics of P‐Rex1 Complexed with Natural Leads Establishes the Protein as an Attractive Target for Therapeutics to Suppress Cancer Metastasis

Phosphatidylinositol 3,4,5‐trisphosphate‐ (PIP3‐) dependent Rac exchanger 1 (P‐Rex1) functions as Rho guanine nucleotide exchange factor and is activated by synergistic activity of Gβγ and PIP3 of the heterotrimeric G protein. P‐Rex1 activates Rac GTPases for regulating cell invasion and migration and promotes metastasis in several human cancers including breast, prostate, and skin cancer. The protein is a promising therapeutic target because of its multifunction roles in human cancers. Herein, the present study attempts to identify selective P‐Rex1 natural inhibitors by targeting PIP3‐binding pocket using large‐size multiple natural molecule libraries. Each library was filtered subsequently in FAF‐Drugs4 based on Lipinski’s rule of five (RO5), toxicity, and filter pan assay interference compounds (PAINS). The output hits were virtually screened at the PIP3‐binding pocket through PyRx AutoDock Vina and cross‐checked by GOLD. The best binders at the PIP3‐binding pocket were prioritized using a comparative analysis of the docking scores. Top‐ranked two compounds with high GOLD fitness score (&gt;80) and lowest AutoDock binding energy (&lt; ‐12.7 kcal/mol) were complexed and deciphered for molecular dynamics along with control‐P‐Rex1 complex to validate compound binding conformation and disclosed binding interaction pattern. Both the systems were seen in good equilibrium, and along the simulation time, the compounds are in strong contact with the P‐Rex1 PIP3‐binding site. Hydrogen bonding analysis towards simulation end identified the formation of 16 and 22 short‐ and long‐distance hydrogen bonds with different percent of occupancy to the PIP3 residues for compound I and compound 2, respectively. Radial distribution function (RDF) analysis of the key hydrogen bonds between the compound and the PIP3 residues demonstrated a strong affinity of the compounds to the mentioned PIP3 pocket. Additionally, MMGB/PBSA energies were performed that confirmed the dominance of Van der Waals energy in complex formation along with favorable contribution from hydrogen bonding. These findings were also cross‐validated by a more robust WaterSwap binding energy predictor, and the results are in good agreement with a strong binding affinity of the compounds for the protein. Lastly, the key contribution of residues in interaction with the compounds was understood by binding free energy decomposition and alanine scanning methods. In short, the results of this study suggest that P‐Rex1 is a good druggable target to suppress cancer metastasis; therefore, the screened druglike molecules of this study need in vitro and in vivo anti‐P‐Rex1 validation and may serve as potent leads to fight cancer.

Energy landscapes on polymerized liquid crystal interfaces.

We measure and model monolayers of concentrated diffusing colloidal probes interacting with polymerized liquid crystal (PLC) planar surfaces. At topological defects in local nematic director profiles at PLC surfaces, we observe time-averaged two-dimensional particle density profiles of diffusing colloidal probes that closely correlate with spatial variations in PLC optical properties. An inverse Monte Carlo analysis of particle concentration profiles yields two-dimensional PLC interfacial energy landscapes on the kT-scale, which is the inherent scale of many interfacial phenomena (e.g., self-assembly, adsorption, diffusion). Energy landscapes are modelled as the superposition of macromolecular repulsion and van der Waals attraction based on an anisotropic dielectric function obtained from the liquid crystal birefringence. Modelled van der Waals landscapes capture most net energy landscape variations and correlate well with experimental PLC director profiles around defects. Some energy landscape variations near PLC defects indicate either additional local repulsive interactions or possibly the need for more rigorous van der Waals models with complete spectral data. These findings demonstrate direct, sensitive measurements of kT-scale van der Waals energy landscapes at PLC interfacial defects and suggest the ability to design interfacial anisotropic materials and van der Waals energy landscapes for colloidal assembly.

Molecular Model Construction and Optimization Study of Gas Coal in the Huainan Mining Area

To construct the macromolecular model of gas coal in the Huainan mining area, 13C nuclear magnetic resonance spectroscopy (13C-NMR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) tests were used to analyze the microstructure characteristics of coal including the aromatic ring type, the linkage mode, and the chemical bonding composition. The model was simulated and optimized by molecular mechanics (MM) and molecular dynamics (MD). The experimental results showed that the coal macromolecular formula in the Huainan mine was expressed as C181H150O9N3. The aromatic ring was dominated by anthracene and phenanthrene. Aliphatic carbon mainly existed in the form of methylene and methine. The oxygen atoms existed in the form of ether−oxygen bonds. The ratio of pyridine nitrogen to pyrrolic nitrogen was 2:1. The molecular simulation results showed the π−π interaction between the aromatic lamellae within the molecule. The van der Waals energy was the major factor of coal molecular structure stability and energy change. The results of the calculated 13C-NMR carbon spectrum and density simulation agreed well with the experimental results. The study provides a scientific and reasonable method for coal macromolecular model prediction and theoretical support for coal spontaneous combustion prevention technology.

A hydrophobic and hierarchical porous resin-based activated carbon modified by g-C3N4 for toluene capture from humid conditions

The synthesis of hydrophobic and hierarchical porous activated carbon (AC) used for toluene capture from a humid atmosphere still remains a challenge. In this work, a novel hydrophobic and hierarchical porous AC was prepared from resorcinol-formaldehyde resin spheres using g-C3N4 as a new pore-forming agent. By the proper participation of g-C3N4, the obtained adsorbent GNHRC-1.5 was endowed with an excellent toluene adsorption capacity (10 mmol/g) under low pressure of P = 0.2 kPa, which was 54% higher than that of nonmodified resin-based AC. By DIH (Difference of Isosteric Heats) prediction, the adsorption selectivity of GNHRC-1.5 to toluene/water was further enhanced to 139.55, higher than that of other reported adsorbents. Toluene breakthrough tests and kinetic analysis showed that GNHRC-1.5 possessed a faster intraparticle diffusion and outstanding reusability, which was ascribed to its a certain amount of mesopores. Grand Canonical Monte Carlo and molecular dynamics simulation were applied to explore the competitive adsorption mechanism of toluene and water vapor from the perspective of pore size and surface functional groups. The results indicated that the competitive adsorption was controlled by Van der Waals energy, intramolecular energy and electrostatic energy. Both the higher content of narrow micropores below 1 nm and carboxyl are not beneficial for toluene adsorption under humid conditions. For GNHRC-1.5, an appropriate micropore distribution, a certain amount of mesopores, and a lower content of oxygen functional groups, afford it excellent adsorption selectivity for toluene and fast adsorption kinetics under humid conditions.

Structural plasticity of omicron BA.5 and BA.2.75 for enhanced ACE-dependent entry into cells

The current study investigated the binding variations among the wilt type, Omicron sub-variants BA.2.75 and BA.5, using protein-protein docking, protein structural graphs (P SG), and molecular simulation methods. HADDOCK predicted docking scores and dissociation constant (KD) revealed tighter binding of these sub-variants in contrast to the WT. Further investigation revealed variations in the hub residues, protein sub-networks, and GlobalMetapath in these variants as compared to the WT. A very unusual dynamic for BA.2.75 and BA.5 was observed, and secondary structure transition can also be witnessed in the loops (44–505). The results show that the flexibility of these three loops is increased by the mutations as an allosteric effect and thus enhances the chances of bonding with the nearby residues to connect and form a stable connection. Furthermore, the additional hydrogen bonding contacts steer the robust binding of these variants in contrast to the wild type. The total binding free energy for the wild type was calculated to be –61.38 kcal/mol, while for BA.2.75 and BA.5 variants the T BE was calculated to be –70.42 kcal/mol and 69.78 kcal/mol, respectively. We observed that the binding of BA.2.75 is steered by the electrostatic interactions while the BA.5 additional contacts are due to the vdW (Van der Waal) energy. From these findings, it can be observed the Spike (S) protein is undergoing structural adjustments to bind efficiently to the hACE2 (human angiotensin-converting enzyme 2) receptor and, in turn, increase entry to the host cells. The current study will aid the development of structure-based drugs against these variants. Communicated by Ramaswamy H. Sarma

Design, Synthesis, α-Amylase/α-Glucosidase Inhibition Assay, Induced Fit Docking Study of New Hybrid Compounds Containing 4H-Pyrano[2,3-d]pyrimidine, 1H-1,2,3-Triazole and D-Glucose Components.

In this study, the click chemistry between N-propargyl derivatives of substituted 4H-pyrano[2,3-d]pyrimidines and tetra-O-acetyl-α-d-glucopyranosyl azide carried out under catalytic conditions using catalyst CuI@Montmorillonite and additive N,N-diisopropylethylamine (DIPEA). The yields of obtained hybrid compounds having 4H-pyrano[2,3-d]pyrimidine connected to 1H-1,2,3-triazole rings were about 85-94 %. All these synthesized hybrid compounds were examined for in vitro α-amylase (with IC50 values in the range of 103.63±1.13 μM to 295.45±1.11 μM) and α-glucosidase (with IC50 values in the range of 45.63±1.14 μM to 184.52±1.15) inhibitory activity. Amongst this series, ethyl ester 8m showed the best inhibitory activity against α-amylase with IC50 of 103.63±1.13 μM, while ethyl ester 8t exhibited the highest activity against α-glucosidase with IC50 of 45.63±1.14 μM. The kinetics of the inhibition of compound 8t showed the competitive α-glucosidase inhibitor property of this compound. Furthermore, the most potent compounds had any cytotoxicity against human normal cells. Induced fit docking and molecular dynamics simulation calculations indicated that the inhibition potential compounds 8m and 8t had the active interactions with the residues in receptors of corresponding tested enzymes. The calculated binding free energy from MM-GBSA approach showed that the major energy components contributed to the active binding of these studied inhibitors, including Coulomb, lipophilic and van der Waals energy. Further, 300 ns MD simulation showed that studied ligand-protein complexes were stable and indicated the structural observations into mode of binding in these complexes.