A threefold approach including quantum chemical, molecular docking and molecular dynamic studies to explore the natural compounds from Centaurea jacea as the potential inhibitors for COVID-19

In the current report, we studied the possible inhibitors of COVID-19 from bioactive constituents of Centaurea jacea using a threefold approach consisting of quantum chemical, molecular docking and molecular dynamic techniques. Centaurea jacea is a perennial herb often used in folk medicines of dermatological complaints and fever. Moreover, anticancer, antioxidant, antibacterial and antiviral properties of its bioactive compounds are also reported. The Mpro (Main proteases) was docked with different compounds of Centaurea jacea through molecular docking. All the studied compounds including apigenin, axillarin, Centaureidin, Cirsiliol, Eupatorin and Isokaempferide, show suitable binding affinities to the binding site of SARS-CoV-2 main protease with their binding energies -6.7 kcal/mol, -7.4 kcal/mol, -7.0 kcal/mol, -5.8 kcal/mol, -6.2 kcal/mol and -6.8 kcal/mol, respectively. Among all studied compounds, axillarin was found to have maximum inhibitor efficiency followed by Centaureidin, Isokaempferide, Apigenin, Eupatorin and Cirsiliol. Our results suggested that axillarin binds with the most crucial catalytic residues CYS145 and HIS41 of the Mpro, moreover axillarin shows 5 hydrogen bond interactions and 5 hydrophobic interactions with various residues of Mpro. Furthermore, the molecular dynamic calculations over 60 ns (6×106 femtosecond) time scale also shown significant insights into the binding effects of axillarin with Mpro of SARS-CoV-2 by imitating protein like aqueous environment. From molecular dynamic calculations, the RMSD and RMSF computations indicate the stability and dynamics of the best docked complex in aqueous environment. The ADME properties and toxicity prediction analysis of axillarin also recommended it as safe drug candidate. Further, in vivo and in vitro investigations are essential to ensure the anti SARS-CoV-2 activity of all bioactive compounds particularly axillarin to encourage preventive use of Centaurea jacea against COVID-19 infections.

Quantum-Chemical Quasi-Docking for Molecular Dynamics Calculations

The quantum quasi-docking procedure is used to compare the docking accuracies of two quantum-chemical semiempirical methods, namely, PM6-D3H4X and PM7. Quantum quasi-docking is an approximation to quantum docking. In quantum docking, it is necessary to search directly for the global minimum of the energy of the protein-ligand complex calculated by the quantum-chemical method. In quantum quasi-docking, firstly, we look for a wide spectrum of low-energy minima, calculated using the MMFF94 force field, and secondly, we recalculate the energies of all these minima using the quantum-chemical method, and among these recalculated energies we determine the lowest energy and the corresponding ligand position. Both PM6-D3H4X and PM7 are novel methods that describe well-dispersion interactions, hydrogen and halogen bonds. The PM6-D3H4X and PM7 methods are used with the COSMO implicit solvent model as it is implemented in the MOPAC program. The comparison is made for 25 high quality protein-ligand complexes. Firstly, the docking positioning accuracies have been compared, and we demonstrated that PM7+COSMO provides better positioning accuracy than PM6-D3H4X. Secondly, we found that PM7+COSMO demonstrates a much higher correlation between the calculated and measured protein–ligand binding enthalpies than PM6-D3H4X. For future quantum docking PM7+COSMO is preferable, but the COSMO model must be improved.

The Influence of Hydrogen Passivation on Conductive Properties of Graphene Nanomesh—Prospect Material for Carbon Nanotubes Growing

Graphene nanomesh (GNM) is one of the most intensively studied materials today. Chemical activity of atoms near GNM’s nanoholes provides favorable adsorption of different atoms and molecules, besides that, GNM is a prospect material for growing carbon nanotubes (CNTs) on its surface. This study calculates the dependence of CNT’s growing parameters on the geometrical form of a nanohole. It was determined by the original methodic that the CNT’s growing from circle nanoholes was the most energetically favorable. Another attractive property of GNM is a tunable gap in its band structure that depends on GNM’s topology. It is found by quantum chemical methods that the passivation of dangling bonds near the hole of hydrogen atoms decreases the conductance of the structure by 2–3.5 times. Controlling the GNM’s conductance may be an important tool for its application in nanoelectronics.

Trivial Excitation Energy Transfer to Carotenoids Is an Unlikely Mechanism for Non-photochemical Quenching in LHCII

Higher plants defend themselves from bursts of intense light via the mechanism of Non-Photochemical Quenching (NPQ). It involves the Photosystem II (PSII) antenna protein (LHCII) adopting a conformation that favors excitation quenching. In recent years several structural models have suggested that quenching proceeds via energy transfer to the optically forbidden and short-lived S1 states of a carotenoid. It was proposed that this pathway was controlled by subtle changes in the relative orientation of a small number of pigments. However, quantum chemical calculations of S1 properties are not trivial and therefore its energy, oscillator strength and lifetime are treated as rather loose parameters. Moreover, the models were based either on a single LHCII crystal structure or Molecular Dynamics (MD) trajectories about a single minimum. Here we try and address these limitations by parameterizing the vibronic structure and relaxation dynamics of lutein in terms of observable quantities, namely its linear absorption (LA), transient absorption (TA) and two-photon excitation (TPE) spectra. We also analyze a number of minima taken from an exhaustive meta-dynamical search of the LHCII free energy surface. We show that trivial, Coulomb-mediated energy transfer to S1 is an unlikely quenching mechanism, with pigment movements insufficiently pronounced to switch the system between quenched and unquenched states. Modulation of S1 energy level as a quenching switch is similarly unlikely. Moreover, the quenching predicted by previous models is possibly an artifact of quantum chemical over-estimation of S1 oscillator strength and the real mechanism likely involves short-range interaction and/or non-trivial inter-molecular states.

DFT Studies and Quantum Chemical Calculations of Benzoyl Thiourea Derivatives Linked with Morpholine and Piperidine for the Evaluation of Antifungal Activity

Herein, we report the density functional study of benzoyl thiourea derivatives linked to morpholine and piperidine to evaluate their antifungal activity. Overall six compounds BTP 1-3 and BTM 4-6 were optimized with DFT using the B3LYP method with 6-31G(d,p) basis set. The molecular geometry, bond lengths, bond angles, atomic charges and HOMO-LUMO energy gap have been investigated. The structural parameters have been compared with the reported experimental results and structure- antifungal activity relationship is explored in details. The calculated results from DFT were discussed using all Quantum chemical parameters of the compounds. Introduction: Benzoyl thiourea derivatives linked with morpholine and piperidine were reported to have good antifungal activity. Objective: To find the correlations between the quantum chemical calculations and the antifungal activity for the benzoyl thiourea derivatives linked with morpholine and piperidine. Method: Optimization was carried out with DFT using B3LYP method utilizing 6-31G(d,p) basis set. Results: A good correlation between the quantum chemical calculations and the antifungal activity for the benzoyl thiourea derivatives linked with morpholine and piperidine was found. Conclusion: The DFT study of benzoyl thiourea derivatives linked to morpholine and piperidine was evaluated for their antifungal activity and it showed good correlations of activity with the quantum chemical parameters.