Rutin as promising drug for the treatment of Parkinson’s disease: an assessment of MAO-B inhibitory potential by docking,molecular dynamics and DFT studies

ABSTRACT

Inhibitors of monoamine oxidase (MAO)-B have been used for many years in the therapy of Parkinson’s disease (PD). Owing to the safety concerns of the currently used agents, the discovery of novel scaffolds is of considerable interest. MAO-B inhibitory potential of rutin, a flavonoid derived from natural sources, has been established in experimental findings. Hence, the current study seeks to examine the interactions between rutin and crystal structure of human MAO-B enzyme. Molecular docking calculations, as well as molecular dynamics simulations, were employed to investigate the binding mode and the stability of the rutin/MAO-B complex. Energies of highest occupied/lowest unoccupied molecular orbitals were computed through DFT studies and used to calculate electron affinity, hardness, chemical potential, electronegativity, and electrophilicity index in order to investigate the capability of these parameters to influence the ligand–receptor interactions. It was found that rutin traverses both the entrance cavity and the substrate cavity, forcing the Ile-199 ‘gate’ to rotate into its open conformation. It results in the fusion of the two cavities of the MAO-B binding site and directly leads to better binding interactions. Results of the current study can be used for lead modification and development of novel drugs for the treatment of PD.     

Theoretical study of the intermolecular potential energy and second virial coefficient in the mixtures of CH4 and Kr gases: a comparison with experimental data

The intermolecular potential energy surface (IPS) in the mixtures of CH₄–Kr gases from ab initio calculations has been explored. The ab initio calculation was performed at the second-order Møller–Plesset perturbation theory (MP₂), with the 6-311+G(2df,2pd) basis set, for three relative orientations of two CH₄–Kr molecules as a function of CH₄–Kr separation distance. In this work, the IPS, U(r), of the CH₄–Kr complex has been investigated, where the vertex (V), edge (E) and face (F) of CH₄ approaches to Kr have been considered. Then, adjustable parameters of the Lennard-Jones and Buckingham potential energy function are fitted to the ab initio MP2/6-311+G(2df,2pd) interaction energies for three different orientations. Assuming a given set of parameters, we theoretically obtained second virial coefficients for the CH₄–Kr system, and compared with the experimental data at different temperatures. Trivial differences can be observed between the experimental and computational results.     

Molecular Mechanics Studies of Molybdenum Disulphide Catalysts Parameterisation of Molybdenum and Sulphur

Abstract

A method for the parameterisation of molybdenum disulphide is presented which reproduces the crystal structure accurately. The method involves calculating parameters such that there is no net force contribution from any individual term of the potential on any atom. Ideal bond lengths and bond angles are taken from the X-ray crystal structure; stretching and bending force constants are calculated from a combination of spectroscopic data and quantum mechanics calculations, whereby the energy function with bond length or bond angle is calculated and fitted with an harmonic potential. For the non-bonded Lennard-Jones parameters, the dispersion coefficient C was calculated by an interpolation of existing published parameters using a multiple regression and then the crystal energy was minimised with respect to the van der Waals radius r₀ using a fixed crystal fragment.

These parameters were tested for various models of the hexagonal and rhombohedral forms of MoS₂. RMS fits between structures minimised with molecular mechanics and experimental models ranged from 0.006 Å to 0.012 Å.     

Water transport through carbon nanotubes with defects

Non-equilibrium molecular dynamics simulations are performed to investigate how changing the number of structural defects in the wall of a (7,7) single-walled carbon nanotube (CNT) affects water transport and internal fluid dynamics. Structural defects are modelled as vacancy sites (missing carbon atoms). We find that, while fluid flow rates exceed continuum expectations, increasing numbers of defects lead to significant reductions in fluid velocity and mass flow rate. The inclusion of such defects causes a reduction in the water density inside the nanotubes and disrupts the nearly frictionless water transport commonly attributed to CNTs.     

Heparan sulfate-protein binding specificity

Heparan sulfate (HS) represents a large class of linear polysaccharides that are required for the function of all mammalian physiological systems. HS is characterized by a repeating disaccharide backbone that is subject to a wide range of modifications, making this class of macromolecules arguably the most information dense in all of biology. The majority of HS functions are associated with the ability to bind and regulate a wide range of proteins. Indeed, recent years have seen an explosion in the discovery of new activities for HS where it is now recognized that this class of glycans functions as co-receptors for growth factors and cytokines, modulates cellular uptake of lipoproteins, regulates protease activity, is critical to amyloid plaque formation, is used by opportunistic pathogens to enter cells, and may even participate in epigenetic regulation. This review will discuss the current state of understanding regarding the specificity of HS-protein binding and will describe the concept that protein binding to HS depends on the overall organization of domains within HS rather than fine structure.     

Hypochlorous acid as a precursor of free radicals in living systems

Hypochlorous acid (HOCl) is produced in the human body by the family of mammalian heme peroxidases, mainly by myeloperoxidase, which is secreted by neutrophils and monocytes at sites of inflammation. This review discusses the reactions that occur between HOCl and the major classes of biologically important molecules (amino acids, proteins, nucleotides, nucleic acids, carbohydrates, lipids, and inorganic substances) to form free radicals. The generation of such free radical intermediates by HOCl and other reactive halogen species is accompanied by the development of halogenative stress, which causes a number of socially important diseases, such as cardiovascular, neurodegenerative, infectious, and other diseases usually associated with inflammatory response and characterized by the appearance of biomarkers of myeloperoxidase and halogenative stress. Investigations aimed at elucidating the mechanisms regulating the activity of enzyme systems that are responsible for the production of reactive halogen species are a crucial step in opening possibilities for control of the development of the body’s inflammatory response.     

Biocatalytic synthesis of conducting polymers and prospects for its application

Enzymatic methods of synthesis of conducting polymers, physicochemical properties of the resulting products, and mechanisms of the reactions are considered. The enzymes involved in oxidative polymerization of monomers are briefly characterized. Examples of practical application of enzymatically synthesized conducting polymers are given.