Critical assessment of popular biomolecular force fields for molecular dynamics simulations of folding and enzymatic activity of main protease of coronavirus SARS-CoV-2.

The main cysteine protease (M) of coronavirus SARS-CoV-2 has become a promising target for computational development in anti-COVID-19 treatments. Here, we benchmarked the performance of six biomolecular molecular dynamics (MD) force fields (OPLS-AA, CHARMM27, CHARMM36, AMBER03, AMBER14SB and GROMOS G54A7) and three water models (TIP3P, TIP4P and SPC) for reproducing the native fold and the enzymatic activity of M as monomeric and dimeric units. The MD sampling up to 1 μs suggested that the proper choice of the force fields and water models plays an essential role in reproducing the tertiary structure and the inter-residue distance between the catalytic dyad His41-Cys145.

Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2.

The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in the world healthcare system. Despite some progress in the creation of antiviral vaccines and mass vaccination of the population, the number of patients continues to grow because of the spread of new SARS-CoV-2 mutations. There is an urgent need for direct-acting drugs capable of suppressing or stopping the main mechanisms of reproduction of the coronavirus SARS-CoV-2.

Insight to the Local Structure of Mixtures of Imidazolium-Based Ionic Liquids and Molecular Solvents from Molecular Dynamics Simulations and Voronoi Analysis.

While the physicochemical properties as well as the NMR and vibration spectroscopic data of the mixtures of ionic liquids (ILs) with molecular solvents undergo a drastic change around the IL mole fraction of 0.2, the local structure of the mixtures pertaining to this behavior remains unclear. In this work, the local structure of 12 mixtures of 1-butyl-3-methylimidazolium cation (Cmim) combined with perfluorinated anions, such as tetrafluoroborate (BF), hexafluorophosphate (PF), trifluoromethylsulfonate (TFO), and bis(trifluoromethanesulfonyl)imide, (TFSI), and aprotic dipolar solvents, such as acetonitrile (AN), propylene carbonate (PC), and gamma butyrolactone (γ-BL) is studied by molecular dynamics simulations in the entire composition range, with an emphasis on the IL mole fractions around 0.

Voronoi Polyhedra as a Tool for the Characterization of Inhomogeneous Distribution in 1-Butyl-3-methylimidazolium Cation-Based Ionic Liquids.

The inhomogeneity distribution in four imidazolium-based ionic liquids (ILs) containing the 1-butyl-3-methylimidazolium (Cmim) cation, coupled with tetrafluoroborate (BF), hexafluorophosphate (PF), bis(trifluoromethanesulfonyl)amide (TFSA), and trifluoromethanesulfonate (TfO) anions, was characterized using Voronoi polyhedra. For this purpose, molecular dynamic simulations have been performed on the isothermal-isobaric () ensemble. We checked the ability of the potential models to reproduce the experimental density, heat of vaporization, and transport properties (diffusion and viscosity) of these ionic liquids.

[The importance of therapeutic muds of the Arasan-Kundyzdy deposit for the development of peloid therapy in Kazakhstan].

Background: To provide the population with inexpensive and effective medical products of domestic production is one of the most important public health tasks. These may include therapeutic muds, the high therapeutic value of which is confirmed by many years of positive experience with peloid therapy. The basis for interest in therapeutic muds is their efficiency in treating many diseases and regularly discovered new opportunities for their use.