We have performed a series of molecular dynamics simulations of aqueous NaCl and KCl solutions at different concentrations, ranging from 0 M to 4.5 M, to investigate the effects of ion concentration on the single-particle, pair, and collective dynamical properties of aqueous electrolyte solutions. The SPC/E model is used for water and the ions are modeled as charged Lennard-Jones particles. The single-particle dynamics is investigated by calculating the self-diffusion coefficients of ions and water molecules and also the orientational relaxation times. The pair dynamics is studied by evaluating the ion–water residence and water–water hydrogen bond time correlation functions. The relaxation of relative velocity autocorrelation function and the cross velocity correlation function of two hydrogen bonded water molecules are also investigated at varying ion concentration. Finally, we explore the collective dynamical properties by calculating the frequency dependent dielectric function and conductivity. It is found that the self and relative diffusion coeffcients decrease and the orientational relaxation times increase with ion concentration. The residence times of water molecules near ions and also the structural relaxation time of water–water hydrogen bonds show an increasing trend as the ion concentration is increased. The dielectric relaxation time is found to decrease with ion concentration for the solutions investigated here. The static conductivity of concentrated solutions shows significant departure from the Nernst–Einstein behavior due to formation of ion pairs. With an increase of frequency, the conductivity first increases substantially and then decreases at very high frequency. The initial increase of conductivity is attributed to the disruption of ion pairs on application of high frequency electric fields.
Coronavirus disease 2019 (COVID-19) is a viral respiratory disease which caused global health emergency and announced as pandemic disease by World Health Organization. Lack of specific drug molecules or treatment strategy against this disease makes it more devastating. Thus, there is an urgent need of effective drug molecules to fight against COVID-19. The main protease (Mpro) of SARS CoV-2, a key component of this viral replication, is considered as a prime target for anti-COVID-19 drug development. In order to find potent Mpro inhibitors, we have selected eight polyphenols from green tea, as these are already known to exert antiviral activity against many RNA viruses. We have elucidated the binding affinities and binding modes between these polyphenols including a well-known Mpro inhibitor N3 (having binding affinity À7.0 kcal/mol) and Mpro using molecular docking studies. All eight polyphenols exhibit good binding affinity toward Mpro (À7.1 to À9.0 kcal/mol). However, only three polyphenols (epigallocatechin gallate, epicatechingallate and gallocatechin-3-gallate) interact strongly with one or both catalytic residues (His41 and Cys145) of Mpro. Molecular dynamics simulations (100 ns) on these three Mpro-polyphenol systems further reveal that these complexes are highly stable, experience less conformational fluctuations and share similar degree of compactness. Estimation of total number of intermolecular H-bond and MM-GBSA analysis affirm the stability of these three Mpro-polyphenol complexes. Pharmacokinetic analysis additionally suggested that these polyphenols possess favorable drug-likeness characteristics. Altogether, our study shows that these three polyphenols can be used as potential inhibitors against SARS CoV-2 Mpro and are promising drug candidates for COVID-19 treatment.
We have carried out a series of molecular dynamics simulations to investigate the dynamics of X(-)-water (X = F, Cl, Br, and I) and water-water hydrogen bonds in aqueous alkali halide solutions at room temperature and also of Cl(-)-water and water-water hydrogen bonds at seven different temperatures ranging from 238 to 318 K. The hydrogen bonds are defined by using a set of configurational criteria with respect to the anion(oxygen)-oxygen and anion(oxygen)-hydrogen distances and the anion(oxygen)-oxygen-hydrogen angle for an anion(water)-water pair. The results of the hydrogen bond dynamics are obtained for two different cutoff values for the angular criterion. In both cases, similar dynamical behavior of the hydrogen bonds is found with respect to their dependence on ion size and temperature. The fluoride ion-water hydrogen bonds are found to break at a much slower rate than water-water hydrogen bonds, while the lifetimes of chloride and bromide ion-water hydrogen bonds are found to be shorter than those of fluoride ion-water ones but still longer than water-water hydrogen bonds. The short-time dynamics of iodide ion-water hydrogen bonds is found to be slightly faster, while its long-time dynamics is found to be slightly slower than the corresponding water-water hydrogen bond dynamics. Correlations of the observed dynamics of anion(water)-water hydrogen bonds with those of rotational and translational diffusion and residence times of water molecules in ion(water) hydration shells are also discussed. With variation of temperature, the lifetimes of both Cl(-)-water and water-water hydrogen bonds are found to show Arrhenius behavior with a slightly higher activation energy for the Cl(-)-water hydrogen bonds.
We have performed a series of molecular dynamics simulations of alkali metal (Li+, Na+, K+, Rb+, and Cs+) and halide (F−, Cl−, Br−, and I−) ions in water at infinite dilution at T=258 K to investigate the effects of ion size on the hydration structure and diffusion of ions in supercooled water. Simulations are also performed at T=298 K in order to compare the results of the hydration structure and diffusion in supercooled water with those in ambient water. With increase of ion size, like in ambient water, in supercooled water also the diffusion coefficients of alkali metal and halide ions are found to fall in different curves with distinct maxima. However, the relative increases of the diffusion coefficients of larger ions compared to those of Li+ and F− are found to be significantly higher in the supercooled water.
The current COVID-19 pandemic is caused by SARS CoV-2. To date, $463,000 people died worldwide due to this disease. Several attempts have been taken in search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro) from SARS CoV-2 plays a vital role in viral replication and thus serves as an important drug target. This Mpro shares a high degree of sequence similarity (>96%) with the same protease from SARS CoV-1 and MERS. It was already reported that Broussonetia papyrifera polyphenols efficiently inhibit the catalytic activity of SARS CoV-1 and MERS Mpro. But whether these polyphenols exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To understand this fact, here we have adopted computational approaches. Polyphenols having proper drug-likeness properties and two repurposed drugs (lopinavir and darunavir; having binding affinity À7.3 to À7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only six polyphenols (broussochalcone A, papyriflavonol A, 3'-(3-methylbut-2-enyl)-3',4',7-trihydroxyflavane, broussoflavan A, kazinol F and kazinol J) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (À7.6 to À8.2 kcal/mol). Molecular dynamic simulations (100 ns) revealed that all Mpro-polyphenol complexes are more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bond and MM-GBSA analysis suggested that these six polyphenols are more potent Mpro inhibitors than the two repurposed drugs (lopinavir and darunavir) and may serve as promising anti-COVID-19 drugs.
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