Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.

Evolutionary adaptation of DHFR via expression of enzyme isoforms with various binding properties and dynamics behavior: a bioinformatics and computational study

We compared the binding properties and dynamics of three experimentally reviewed isoforms of human dihydrofolate reductase (DHFR). The cytoplasmic variants including isoforms1 and 2 (iso1 and iso2) are produced by alternative splicing; while the mitochondrial form is located in the mitochondria. The iso1 as the canonical sequence contains 187 residues, and iso2 differs from the iso1, where it has 1–52 residues missing at the N-terminus of canonical sequence. Here, the structural models of the iso2 and mitochondrial forms were constructed by the MODELLER program using the crystal structure of the iso1 as the template. Bioinformatics analysis on ligand-bearing structures demonstrates that mitochondrial variant forms more stable complex with ligands compared with iso1 and 2, indicating their different binding properties. The root mean square fluctuation (RMSF) data suggest that C-terminus of iso1 contains two representative highly flexible fragments, while iso2 contains a highly flexible fragment at N-terminus end. Interestingly, both ends of mitochondrial variant have a degree of rigidity. Finally, the observation of differences in structural dynamics and binding properties predicts that the simultaneous existence of enzyme isoforms is a way to increase the speed of the enzyme maneuver in response to various environmental conditions. This prediction needs to be tested experimentally.

The Inhibitory Effect of Some Natural Bioactive D-Glucopyranoside Derivatives against SARS-CoV-2 Main Protease (Mpro) and Spike Protease (Spro)

Outbreak of coronavirus seems to have exacerbated across the globe, but drugs have not been discovered till now. Due to having the antiviral activity of D-glucopyranoside derivatives, this study was designed to examine as the inhibitor by in sillico study against the main protease (Mpro) and Spike protease (Spro) of SARS-CoV-2. First, these derivatives were optimised by Density Functional Theory (DFT). The observation of this study was monitored by molecular docking tools calculating the binding affinities. Afterwards, the ligand interaction with protein was accounted for selecting the how to bind of active sites of the protein. Next, the root means square deviation (RMSD) and root mean square fluctuation (RMSF) were illustrated for determining the stability of the docked complex. Finally, AMDET properties were calculated as well as the Lipisinki rule. All of the derivates showed a binding affinity more than -6.0 kcal/mol while derivatives 2, 3, and 9 were the best-bonded scoring inhibitor against Mpro and Spro. In addition, the chemical descriptors were more supportive tools as an inhibitor, and the Lipisinki rule was satisfied for maximum molecules as a drug. Besides, D-glucopyranoside derivatives may be predicted that they are non-carcinogenic and low toxic for both aquatic and non-aquatic species.

In Silico Evaluation of the Structural Dynamics Beta-Amylase from Sweet Potato (Ipomoea batatas)

Background: Sweet potato tubers are invaluable crop that could serve both dietary and industrial purposes owing to its high β-amylase content. β-amylases play essential role in plant carbohydrate metabolism as well as in many industrial applications such as the malting process in the brewing and distilling industries. Aim: This study aims at better understanding of the evolutionary and molecular properties, and structural dynamics of β-amylase of sweet potato using in silico approach. Methodology: 16 of the 250 sequences that are at least 69% identity to the query sequence (P10537) were manually selected from UniProt database for further analysis. Result: It has theoretical isoelectric point of 4.97 and molecular weight of 56 kDa. The root-mean-square fluctuation (RMSF) of sweet potato β-amylase showed possible conservation of the amino acid residues 105-130 and 260-345, with highest fluctuation in C-terminal loop (residues 443-498). The catalytic role of Glu187 and Thr344 in β-amylase of sweet potato has been elucidated, and it provided the missing link in the previously available mechanisms, while Cys96 is essential for the inactivation of enzyme activity. Conclusion: Elucidation of molecular mechanisms of expression and catalytic activity, together with the understanding of physicochemical properties of β-amylase from sweet potato will help in development of useful applications that are of industrial importance.

Disorder Classification of the Vibrational Spectra of Modern Glasses

Using the coherent-potential approximation in heterogeneous-elasticity theory with a log-normal distribution of elastic constants for the description of the Raman spectrum and the temperature dependence of the specifi?c heat, we are able to reconstruct the vibrational density of states and characteristic descriptors of the elastic heterogeneity of a wide range of glassy materials. These descriptors are the non-affi?ne contribution to the shear modulus, the mean-square fluctuation of the local elasticity, and its correlation length. They enable a physical classification scheme for disorder in modern, industrially relevant glass materials. <br><div>We apply our procedure to a broad range of real-world glass compositions, including metallic,oxide, chalcogenide, hybrid and polymer glasses. Universal relationships between the descriptors on the one side, and the height and frequency position of the boson peak, the Poisson ratio and theliquid fragility index on the other side are established.</div>

Disorder Classification of the Vibrational Spectra of Modern Glasses

Using the coherent-potential approximation in heterogeneous-elasticity theory with a log-normal distribution of elastic constants for the description of the Raman spectrum and the temperature dependence of the specifi?c heat, we are able to reconstruct the vibrational density of states and characteristic descriptors of the elastic heterogeneity of a wide range of glassy materials. These descriptors are the non-affi?ne contribution to the shear modulus, the mean-square fluctuation of the local elasticity, and its correlation length. They enable a physical classification scheme for disorder in modern, industrially relevant glass materials. <br><div>We apply our procedure to a broad range of real-world glass compositions, including metallic,oxide, chalcogenide, hybrid and polymer glasses. Universal relationships between the descriptors on the one side, and the height and frequency position of the boson peak, the Poisson ratio and theliquid fragility index on the other side are established.</div>

Understanding The Mechanism of Mutant HIV-1 Protease Resistance Against Darunavir Using Molecular Dynamic Study

The human immunodeficiency virus type 1 protease (HIV-1 PR) is an important enzyme in life cycle of the HIV virus. It cleaves inactive pre-proteins of the virus and changes them into active proteins. Darunavir suppresses the wild type HIV-1 PR (WT-Pr) activity, but can’t inhibit the mutant resistant forms (MUT-Pr). Increasing knowledge about the resistance mechanism can be helpful for designing of more effective inhibitors. In this study, the mechanism of resistance of Ile47val and Ile54Met MUT-Pr strain against Darunavir was investigated. For this purpose, complexes of Darunavir with WT-Pr (WT-Pr-D) and MUT-Pr (MUT-Pr-D) were simulated for 200 ns and structure, dynamic and energetic properties of both simulations were investigated based on essential dynamics (principal component analysis (PCA)), root mean square fluctuation (RMSF), radial distribution function (RDF), molecular mechanics/Poisson Boltzman surface area (MM/PBSA) energies and etc. Our data revealed that mutations increased the flap tips flexibility and increased the active-site space, probably due to the reduction in hydrophobic forces. So, the protease’s conformation changed from closed state to semi-open state. Formation of semi open structure along with a reduction in van der Waals interactions and hydrogen bonds with Darunavir facilitates disjunction of Darunavir from the active-site in MUT-Pr-D.

The Effect of Turbulence on the Accretional Growth of Graupel

Wind tunnel experiments were carried out to investigate the influence of turbulence on the collection kernel of graupel. The collection kernel defines the growth rate of a graupel accreting supercooled droplets as it falls through a cloud. The ambient conditions were similar to those occurring typically in the mixed-phase zone of convective clouds, that is, at temperatures between −7° and −16°C and with liquid water contents from 0.5 to 1.3 g m−3. Tethered spherical collectors with radii between 220 and 340 μm were exposed in a flow carrying supercooled droplets with a mean volume radius of 10 μm. The vertical root-mean-square fluctuation velocity, the dissipation rate, and the Taylor-microscale Reynolds number of the turbulent flow were determined as urms = 0.13 m s−1, ε = 0.13 m2 s−3, and Rλ = 48, respectively. The collection kernels of tethered graupel grown under laminar and turbulent conditions revealed no measurable difference, indicating that turbulence has no effect on the growth of graupel in the investigated size range. A comparison of laminar collection kernels to theoretically calculated values from a continuous growth model showed that graupel growth is strongly dominated by the fast increase of the radius due to the accretion of rime ice with low density. It is assumed that, compared to a water drop growing by collision and coalescence, this causes a fast increase in the swept volume overcompensating all other effects such as the self-induced stochastic movements due to surface roughness and latent heat release, as well as the possible influence of the flow’s small-scale turbulence.

Hyperoxidation of Peroxiredoxin 6 Induces Alteration from Dimeric to Oligomeric State

Peroxiredoxins(Prdx), the family of non-selenium glutathione peroxidases, are important antioxidant enzymes that defend our system from the toxic reactive oxygen species (ROS). They are thiol-based peroxidases that utilize self-oxidation of their peroxidatic cysteine (Cp) group to reduce peroxides and peroxidized biomolecules. However, because of its high affinity for hydrogen peroxide this peroxidatic cysteine moiety is extremely susceptible to hyperoxidation, forming peroxidase inactive sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) derivatives. With the exception of peroxiredoxin 6 (Prdx6), hyperoxidized sulfinic forms of Prdx can be reversed to restore peroxidase activity by the ATP-dependent enzyme sulfiredoxin. Interestingly, hyperoxidized Prdx6 protein seems to have physiological significance as hyperoxidation has been reported to dramatically upregulate its calcium independent phospholipase A2 activity. Using biochemical studies and molecular dynamic (MD) simulation, we investigated the roles of thermodynamic, structural and internal flexibility of Prdx6 to comprehend the structural alteration of the protein in the oxidized state. We observed the loosening of the hydrophobic core of the enzyme in its secondary and tertiary structures. These changes do not affect the internal dynamics of the protein (as indicated by root-mean-square deviation, RMSD and root mean square fluctuation, RMSF plots). Native-PAGE and dynamic light scattering experiments revealed the formation of higher oligomers of Prdx6 under hyperoxidation. Our study demonstrates that post translational modification (like hyperoxidation) in Prdx6 can result in major alterations of its multimeric status.

A Model for Fuel Spray Formation with Atomizing Air

The formation of a liquid spray emanating from a nozzle in the presence of atomizing air was studied using a computational model approach that accounted for the deformation and break up of droplets. Particular attention was given to the formation of sprays under non-swirling flow conditions. The instantaneous fluctuating fluid velocity and velocity gradient components were evaluated with the use of a probability density function (PDF)-based Langevin equation. Motions of atomized fuel droplets were analyzed, and ensemble and time averaging were used for evaluating the statistical properties of the spray. Effects of shape change of droplets, and their breakup, as well as evaporation, were included in the model. The simulation results showed that the mean-square fluctuation velocities of the droplets vary significantly with their size and shape. Furthermore, the mean-square fluctuation velocities of the evaporating droplet differed somewhat from non-evaporating droplets. Droplet turbulence diffusivities, however, were found to be close to the diffusivity of fluid point particles. The droplet velocity, concentration, and size of the simulated spray were compared with the experimental data and reasonable agreement was found.